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T Kühne

Publications and source records attributed to T Kühne.

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

Neonatal platelet physiology and pathophysiology.

Platelets contribute to primary haemostatic events and are closely linked to plasmatic coagulation. Their function is highly dependent not only on their number but also on their integral physiology. In comparison with adults or children, the haemostasis of newborn infants, although physiological, is characterized by a reduced functional reserve capacity leading to the rapid occurrence of bleeding disorders especially in the presence of additional risk factors such as prematurity, asphyxia, or infection. Morphological and biochemical differences reflect an immature cellular stage which results in platelet hyporeactivity and contributes to the reduced capacity of the neonatal haemostatic system. Additionally acquired and inherited platelet disorders markedly affect platelet function. Hence assessment of neonatal platelet physiology may supply important information, however, no adequate screening tests are currently available, and technical difficulties of blood sampling limit the value of laboratory testing. Evaluation of the neonatal platelet function is highly dependent on individual laboratory results and it is advisable to perform complex diagnostic procedures with the collaboration of specialists experienced in neonatal haematology. With the advent of new technology such as platelet flow cytometry more adequate tools are available, although still reserved for specialized laboratories, thus awaiting their clinical significance. The role of maternal influences on neonatal platelet function must be always considered. Thus, neonatal platelet physiology and pathophysiology is complex and require more studies and experience.

Blood Platelet Disorders↗
PubMed1998

Management of children with acute and chronic immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is divided in an acute and chronic form based on the duration of the disease. Persistence of thrombocytopenia for more than 6 months defines chronic ITP. The disease occurs in both children and adults with acute ITP as the predominant form of childhood and chronic ITP occurring in approximately 20% of children and almost all adult patients. The diagnostic procedures and the therapeutic consequences are discussed with respect to the many open and unresolved questions recently identified by a panel of pediatric and adult hematologists on behalf of The American Society of Hematology. Research activities with identification of priorities are important to better understand the disease resulting in an optimal evidence-based management of children and adults with ITP.

Acute Disease↗
PubMed1998

Two consecutive pregnancies and deliveries in a patient with von Willebrand's disease type 3.

Pregnancy and delivery are critical events in women with von Willebrand's disease type 3. Prophylactic treatment for delivery and early postpartum period is recommended. Vaginal delivery is considered safe. However, experience is based on rare case reports. We report the management of two pregnancies and successful deliveries in a woman with von Willebrand's disease type 3.

Adult↗
PubMed1998

[Cardiac MR flowmetry: experimental validation and results in patients with operated heart defects].

PURPOSE: A flow-sensitive MR sequence (phase-contrast technique) was evaluated in phantom studies with regard to factors influencing measurements and correctness of results. The sequence was additionally used for functional evaluation of operated congenital heart disease. METHODS: Pulsatile and constant flow were produced with the help of a phantom. Influence of angulation, range and vessel bending was evaluated. An examination protocol was developed from the results. 35 patients with surgically repaired congenital heart disease or without repair were examined. RESULTS: A range preset below the actual flow velocity as well as angulation of more than 20 degrees were isolated as main pitfalls in MR flowmetry. In addition to morphological MR findings flow measurements were possible in 11 patients at vessel sites which were not or not completely suited for examination by Doppler ultrasound. CONCLUSION: The evaluated phase-contrast technique allows for fast and reliable flow quantification if the influences identified in phantom studies are considered.

Blood Flow Velocity↗
PubMed1998

Chronic immune thrombocytopenic purpura in childhood.

Immune thrombocytopenic purpura (ITP) is a bleeding disorder and is traditionally divided in acute and chronic forms based on the duration of the disease. Chronic ITP is characterized by a persistence of thrombocytopenia for more than 6 months. Ten to 20% of children with ITP and almost all adults will develop the chronic condition. Pathophysiology of chronic ITP suggests an autoimmune process and a dysregulated immune response. There are no risk factors to predict the clinical course of ITP. Controlled clinical trials are needed to clarify many diagnostic and therapeutic aspects of chronic ITP, as recently stated by a panel of pediatric and adult hematologists on behalf of The American Society of Hematology (ASH). In this article, we will focus on pathophysiological, diagnostic, and management aspects of chronic childhood ITP.

Child↗
PubMed1998

Molecular diagnosis of Ewing tumors: improved detection of EWS-FLI-1 and EWS-ERG chimeric transcripts and rapid determination of exon combinations.

Most Ewing tumors (ET), including Ewing sarcomas, peripheral primitive neuroectodermal tumors (PNET), and Askin's tumors, can be defined according to the specific chromosomal translocations t(11;22)(q24;q12) (EWS-FLI-1) or t(21;22)(q21;q12) (EWS-ERG). Detection of the chimeric RNA transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) has greatly facilitated the diagnosis of ET. Because of variable chromosomal breakpoint locations, however, the EWS gene fusions with FLI-1 and ERG genes are highly heterogenous, resulting in different sizes of the amplification products. To improve the diagnostic usefulness of the RT-PCR assay, we have developed an assay to detect chimeric mRNA transcripts by nested RT-PCR, followed by digestion of the PCR fragments with three different restriction endonucleases. This allows confirmation of the specificity of the PCR product and provides a rapid method to determine the combination of exons present in a transcript. In the 12 Ewing tumors tested, five different exon combinations were detected. In nine repeat biopsies of four patients, the case-specific translocation remained unchanged. One additional central PNET had no ET-specific translocation. In conclusion, the suggested combination of RT-PCR and restriction analysis of the PCR products allows a rapid and specific determination of ET-specific translocations.

Adolescent↗
PubMed1998

Immune thrombocytopenic purpura ITP.

Immune thrombocytopenic purpura ITP is characterized by early platelet destruction due to an imbalanced immune response. In acute ITP, a transient increase of HLA-DR molecules has been detected while in individuals with chronic ITP, in addition, increased serum concentrations of IL-2 and other cytokines reflecting in vivo T-cell activation have been observed. Clinically, the hemorrhagic manifestation of ITP rather than the platelet count should define the indication for active intervention. In a staging system a patient with stage III has bleeding signs and platelet counts below 10 or 20 x 10(9)/L and needs treatment, a patient with stage II should be treated on an individual level (prevention of bleeding) and a patient with stage I (no bleeding, platelet count above 50 x 10(9)/L) should be observed only.

Adolescent↗
PubMed1998

Current management issues of childhood and adult immune thrombocytopenic purpura (ITP).

The management of acute and chronic immune thrombocytopenic purpura (ITP) of children differs in many aspects from that of adults. Current paediatric and adult treatment options are discussed in this review in the light of the recently published practice guidelines for the diagnosis and treatment of ITP issued by a panel of paediatric and adult haematologists on behalf of the American Society of Hematology. Uncontrolled rather than controlled randomized studies often represent the basis for treatment decisions. Important issues in improving the management of patients with ITP include the identification of research priorities resulting in controlled clinical trials with well-defined study endpoints, the logistics and coordination of research activities and their presentation at international meetings.

Acute Disease↗
PubMed1997

Platelet and immune responses to oral cyclic dexamethasone therapy in childhood chronic immune thrombocytopenic purpura.

OBJECTIVE: To examine the effectiveness of cyclic oral high-dose (HD) dexamethasone therapy in pediatric patients with chronic immune thrombocytopenic purpura (ITP), which has been reported to cause complete remission in adults with chronic ITP. STUDY DESIGN: Eleven children with primary chronic ITP, with a median disease duration of 28 months (range, 6 to 120 months), were treated with cycles of HD dexamethasone therapy. RESULTS: Excellent short-term responses (initial platelet counts < or = 50 x 10(9)/L, increasing to > 100 x 10(9)/L within 72 hours of completion of an HD dexamethasone cycle) were observed in 78% of 41 cycles. Long-term effects include one complete response (platelet count > or = 150 x 10(9)/L) and three partial responses (platelet count > or = 50 and < 150 x 10(9)/L) in 11 children followed for 6 or more months after completing cyclic HD dexamethasone therapy. Because side effects were substantial, three children did not complete their sixth treatment cycle. At day 6 of treatment, B lymphocytes were significantly increased (p = 0.005). CONCLUSIONS: Dexamethasone, given orally in high doses, is an effective drug in achieving short-term platelet responses, but it induced long-term remissions in fewer than half of the children with well-established chronic ITP. Its effect on B lymphocytes requires further elucidation. A prospective, controlled study will be needed to establish whether cyclic HD dexamethasone therapy can alter the natural history of children with early chronic ITP and thus avoid splenectomy.

Administration, Oral↗
PubMed1997

Immunologic aspects in the pathogenesis and treatment of immune thrombocytopenic purpura in children.

Immune thrombocytopenic purpura (ITP) is either a transient or a chronic bleeding disorder characterized by an unbalanced immune response due to inflammation (ie, infection, autoimmunity). There is new evidence arguing for an immune-mediated mechanism operative in ITP-increased HLA-DR expression, defects in cellular and humoral immunity, and specific autoantibody production. Moreover, different forms of ITP may be associated with specific alterations in the immune response. New immunosupportive modalities emphasize biologic interventions as a therapeutic strategy for autoimmune disorders. Practical guidelines for the diagnosis and treatment of ITP were recently established by the American Society of Hematology. These recommendations will substantially influence patient care and future research.

Antibody Formation↗
PubMed1996

Platelet-surface glycoproteins in healthy and preeclamptic mothers and their newborn infants.

Preeclampsia, a common complication of pregnancy, contributes significantly to maternal and fetal morbidity and mortality. It may lead to both quantitative and qualitative defects of maternal and neonatal platelets. In this prospective study, flow cytometry has been used to study expression of platelet-surface glycoproteins (GPs) on maternal and neonatal platelets of both healthy and preeclamptic subjects. We studied 15 preeclamptic women, 20-44 y of age, and their newborns (median gestational age, 32 wk; range, 26-38) and seven healthy women (aged 26-41 y) and their healthy newborns (median gestational age, 38 wk; range, 38-42). Compared with their healthy and preeclamptic mothers, resting platelets from neonates expressed significantly less CD41 and CD9. Thrombin activation resulted in significant increases in platelet-surface expression of CD62P, CD63, CD41, CD9, and CD36 in neonates and their healthy mothers. Compared with neonates of healthy mothers, platelets from neonates of preeclamptic mothers expressed lower levels of CD62P, CD63, CD9, and CD36 on activated platelets. These findings suggest that preeclampsia influences the expression of platelet-surface GPs on neonatal and maternal platelets, which may affect platelet function, leading to an additional risk for bleeding in thrombocytopenic neonates of mothers with preeclampsia.

Adult↗
PubMed1995

Flow cytometric evaluation of platelet activation in blood collected into EDTA vs. Diatube-H, a sodium citrate solution supplemented with theophylline, adenosine, and dipyridamole.

With platelet activation, there is modulation of platelet surface molecule expression. In flow cytometric analyses of in vivo platelet activation, results are often confounded by activation induced in vitro by the preparative procedures. It is particularly important therefore to prevent or retard platelet activation as soon as possible after withdrawal of the blood sample. Taking blood into paraformaldehyde, or fixing the cells with paraformaldehyde as soon as possible after withdrawal, has been employed to prevent platelet activation in vitro, but paraformaldehyde-fixed platelets cannot be further used in functional studies. We investigated the efficacy of Diatube-H, a commercially available combination of platelet antagonists (theophylline, adenosine, and dipyridamole), in preventing or retarding platelet activation in vitro, along with its effects on modulation of platelet membrane glycoproteins (GP) and adhesion molecules. In contrast to blood taken into EDTA, blood taken into Diatube-H vacutainer tubes could be stored at room temperature for up to 4 hr prior to paraformaldehyde fixation without significant in vitro platelet activation, as measured by CD62P, CD63 and modulation of GPIb and GPIIbIIIa surface expression. Hence, paraformaldehyde fixation could be deferred for several hours, permitting transport of samples from distant sites. Studies of thrombin-induced platelet activation indicated that platelets taken into Diatube-H remained functional i.e. were able to be activated. Expression of the CD29, CD49b and CD31 adhesion molecules on the platelet surface was unaffected by storage in Diatube-H. The results suggest that Diatube-H may be a useful reagent for flow cytometric studies of platelets when the samples cannot be processed immediately.

Adenosine↗
PubMed1995

In vitro transcripts of a full-length cDNA of a naturally deleted RNA2 of barley mild mosaic virus (BaMMV) replicate in BaMMV-infected plants.

The RNA2 of a German isolate of the bipartite barley mild mosaic bymovirus (BaMMV-ASL1) is 3524 nucleotides long excluding the 3'-terminal poly(A) tail. The isolate was propagated by mechanical inoculation for several years. Electrophoretic comparison of viral nucleic acids during this period revealed that a spontaneous reduction in the length of the RNA2 occurred, resulting in the isolate BaMMV-ASL1a. The deleted RNA2 of BaMMV lacked a fragment that was 630 nucleotides long. The deletion occurred in the 3' half of the single open reading frame (ORF) found in RNA2; this ORF encodes a polyprotein that has a molecular mass of 98 kDa, which is assumed to be processed autocatalytically into proteins of 25 kDa and 73 kDa. A full-length cDNA of the deleted RNA2 was synthesized and cloned under the control of the phage T7 promoter. In vitro transcripts of the BaMMV-ASL1a clone replicated in barley plants after co-inoculation with a wild-type-like isolate of BaMMV. The deletions in RNA2 of BaMMV-ASL1a and those of a number of other isolates that were examined were found to affect a domain of the putative 73 kDa protein that is obviously not essential for replication but may be important for the transmission of BaMMV by its natural vector Polymyxa graminis.

Base Sequence↗