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S Haas

Publications and source records attributed to S Haas.

At least 19 recordsLinked to original sources
PubMed2001

Order by disorder from nonmagnetic impurities in a two-dimensional quantum spin liquid.

We consider doping of nonmagnetic impurities in the spin-1/2, 1/5-depleted square lattice. This structure, whose undoped phase diagram offers both magnetically ordered and spin-liquid ground states, is realized physically in CaV4O9. Doping into the ordered phase results in a progressive loss of order, which becomes complete at the percolation threshold. By contrast, doping into the spin liquids creates a phase of weak but long-ranged antiferromagnetic order, a true order-by-disorder phenomenon. We study the phase diagram of the doped system by computing the static susceptibility and staggered magnetization using a stochastic series-expansion quantum Monte Carlo technique.

Journal Article↗
PubMed2000

Quasiparticle bound states around impurities in d(x(2)-y(2))-wave superconductors

Zn and Ni impurities in the hole-doped high-temperature superconductors are known to have strong effects on thermodynamic and transport properties. A recent scanning tunneling microscope study of Zn-doped Bi2212 [S. H. Pan et al., Nature (London) 403, 746 (2000)] has provided high-resolution images of the local density of states around nonmagnetic impurities in d(x(2)-y(2))-wave superconductors. These pictures contain detailed information about the spinor wave functions u(r) and v(r) of bound states with energy E0 approximately Delta/30, centered at the Zn sites. We show that this type of wave function follows from the solutions of the Bogoliubov-de Gennes equations for d(x(2)-y(2))-wave superconductors.

Journal Article↗
PubMed2000

Clinical consequences of molecular diagnosis in families with mismatch repair gene germline mutations.

Hereditary nonpolyposis colorectal cancer (HNPCC), clinically defined by the Amsterdam criteria, is associated with mismatch repair gene germline mutations. This study was performed to evaluate the efficiency of combined clinical and molecular diagnostics in identifying carriers of a mutated gene in families meeting criteria of the Bethesda guidelines and to examine the influence of molecular diagnosis on clinical decision-making in carriers and noncarriers. Seventy-two patients meeting criteria of the Bethesda guidelines were tested for microsatellite instabilities (MSI). MSI-H tumors were found in 38 (52.8%) index patients. Complete sequencing of hMLH1 and hMSH2 in 38 MSI-H patients and of hMSH6 in one of these patients revealed 15 pathogenic germline mutations, including three novel mutations, and three novel unclassified germline variants. Twelve of the 15 pathogenic mutations were found in patients fulfilling the Amsterdam I/II criteria. Surgical and genetic counseling was offered to the affected families; as a result of molecular diagnosis in the 15 families, 26 index patients and affected carriers and 8 asymptomatic carriers of a mutated mismatch repair gene were included in the surveillance program, and 26 noncarriers were excluded from this program. Although germline mutations are detected in only 20.8% of patients fulfilling criteria of the Bethesda guidelines, family history and MSI-H tumor classification are both strong indicators for germline mutations in hMSH2, hMLH1, and hMSH6 genes, resulting in a 51.9% mutation detection rate. Identification of individual mutation status allows clear-cut decisions on whether or not inclusion in surveillance programs is indicated.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Effects of recombinant human growth hormone in catabolic adults with chronic renal failure.

Growth hormone (GH) has been used for the treatment of catabolism in a few pilot studies and in two placebo-controlled studies of 6 months duration. Treatment with GH in doses of 2-4 IU/m2/day (0.67-1.33 mg/m2/day) resulted in clear anabolic effects and a significant change in body composition. Lean body mass increased by more than 3 kg within 6 months, whereas fat mass was decreased by the same amount, resulting in a constant total body weight. As there were no major side-effects, controlled long-term studies are justified.

Adult↗
PubMed2000

[Therapy of venous thromboembolism with low-molecular-weight heparins].

Low-molecular-weight heparins, nowadays already widely used for the prevention of thromboembolism, have now also become available for the treatment of deep-vein thrombosis. This article should serve to explain the rationale for this development and to demonstrate the clinically relevant advantages of the use of low-molecular-weight heparins. After briefly describing the characteristic properties of heparins the most relevant studies comparing the use of low-molecular-weight heparin versus unfractionated heparin for the treatment of thromboembolism are discussed. In conclusion, clinical trials suggest that low-molecular-weight heparins given subcutaneously can replace the hitherto standard intravenous application of unfractionated heparin in the initial treatment of deep-vein thrombosis, granting equal or even better efficacy and potentially lower rates of adverse side effects. Furthermore, the simplicity of this therapeutic regime allows for treatment of patients at home, thus offering patients mobility and also reducing the cost of treatment.

Anticoagulants↗
PubMed2000

Interaction between the LMWH reviparin and aspirin in healthy volunteers.

AIMS: To investigate potential interactions between reviparin and acetylsalicylic acid (ASA 300 mg o.d. from day 1-5). METHODS: In an open, randomized, three-way-cross over study nine healthy volunteers received reviparin (s.c. injection of 6300 anti-Xa units) or placebo from days 3 to 5 and acetylsalicylic acid (ASA 300 mg) or placebo from days 1 to 5. Assessments included bleeding time (BT), collagen (1 microg ml-1) induced platelet aggregation (CAG), heptest, plasma antifactor Xa-activity and activated partial thromboplastin time (aPTT). RESULTS: Median bleeding time at day 5 was 5.5 min after reverparin alone and after ASA alone and was 9.6 min after the combination of reviparin and ASA. ASA treatment reduced CAG from 84% to 40 to 50% of Amax; values after combined treatment of reviparin with ASA were not different from those after ASA alone. aPTT was prolonged to 32 s after reviparin; this effect was not modified if subjects received ASA. Combined treatment with ASA and reviparin had no effect on plasma anti-Xa-activity and heptest compared with reviparin alone. CONCLUSIONS: We could not entirely exclude a small interaction between reviparin and ASA on bleeding time, but the effect is probably without clinical significance.

Adult↗
PubMed2000

Recommendations for prophylaxis of venous thromboembolism: International Consensus and the American College of Chest Physicians Fifth Consensus Conference on antithrombotic therapy.

The primary purpose of a Consensus Conference is to provide informed guidance on treatment decisions, assisting clinicians to make the optimal therapeutic choice for the patient, and providing protection against unjustified malpractice actions. The First American College of Chest Physicians (ACCP) Consensus Conference took place in 1985 and, using a systematic approach, provided recommendations for antithrombotic therapy based on published studies, and graded those recommendations on the level of clinical evidence. The European Consensus Conference was convened in 1991 to build on this process. During this period, the main developments included the introduction and widespread use of new thromboprophylactic agents such as low-molecular-weight heparins, and improved risk assessment, including an awareness that out-patients and general medical patients may also be at risk. Subsequently, the recommendations have been carefully reviewed and updated by experts who represent the extensive range of opinions in the field. The latest International Consensus Statement was published in 1997, and the most recent ACCP Consensus in 1998 and they provide extensive practice guidelines in the management of venous thromboembolism.

Arthroplasty, Replacement, Hip↗
PubMed2000

Deep vein thrombosis: beyond the operating table.

Deep vein thrombosis (DVT) is of clinical importance and carries the short-term risk of pulmonary embolism. Patients undergoing orthopedic surgery are at particular risk of DVT. Pharmacological prophylaxis to prevent thromboembolic events has become standard practice in this patient group. However, DVT may also lead to long-term venous insufficiency, causing disabling symptoms of swelling, chronic pain, and skin ulceration, imposing substantial health-care costs. Prevention of these long-term sequelae of DVT, termed post-thrombotic syndrome (PTS), may be of equal or even greater clinical, economic, and medicolegal significance than avoidance of the short-term effects. Surveys suggest that PTS is present in 30%-70% of patients, 5 years after an initial symptomatic or asymptomatic, proximal or distal DVT. Post-thrombotic syndrome is not reliably prevented by treatment of the initial DVT with anticoagulant therapy or thrombolysis. Therefore, prevention of DVT is the only effective approach to PTS prevention. Pharmacological thromboprophylaxis prevents venographically proven DVT in patients following orthopedic surgery, and is now recommended by North American and European consensus statements. Uncertainties remain, however, regarding the optimal duration of postsurgical prophylaxis.

Anticoagulants↗
PubMed2000

The inhibitory potency and selectivity of arginine substrate site nitric-oxide synthase inhibitors is solely determined by their affinity toward the different isoenzymes.

We have investigated various nitric oxide (NO) synthase inhibitors for their affinity and selectivity toward the three human isoenzymes in radioligand binding experiments. Therefore, we developed the new radioligand [(3)H]2-amino-4-picoline to measure binding of these compounds to the three human NO synthase (NOS) isoenzymes. Aminopicoline is a potent and nonselective inhibitor of all three isoforms. [(3)H]2-amino-4-picoline bound saturably and with high affinity to human NOSs. Affinity constants (K(D) values) of 59, 111, and 136 nM were obtained for the inducible, neuronal, and endothelial NOS isoforms (iNOS, nNOS, eNOS). Binding of [(3)H]2-amino-4-picoline was competitive with the substrate arginine. From all the inhibitors tested, AMT (2-amino-5, 6-dihydro-6-methyl-4H-1,3-thiazine hydrochloride) showed the highest affinity and no selectivity. L-NIL [L-N(6)-(1-Iminoethyl)lysine hydrochloride] and aminoguanidine were moderately iNOS-selective while L-NA (N(G)-nitro-L-arginine) and L-NAME (N(G)-nitro-L-arginine methyl ester hydrochloride) showed selectivity toward the constitutive isoforms. High iNOS versus eNOS selectivity was found for 1400W, whereas several isothiourea derivatives and 1400W displayed moderate n- versus eNOS selectivity. To relate the affinity of these compounds to their inhibitory potency, we measured the inhibitory potency under almost identical conditions using a new microtiter plate assay. The inhibitory potency of selective and nonselective NOS inhibitors was almost exactly mirrored by their affinity toward the different isoenzymes. Highly significant correlations were obtained between the potency of enzyme inhibition and the inhibition of [(3)H]2-amino-4-picoline binding for all three isoenzymes. These data show that the potency and selectivity of NOS inhibitors are solely determined by their affinity toward the different isoforms. Furthermore, these data identify the new radioligand [(3)H]2-amino-4-picoline as a very useful radiolabel for the investigation of the substrate binding site of all three isoforms.

Arginine↗
PubMed1999

[Prognostic significance of cell-cycle regulatory proteins for outcome after primary radiochemotherapy in patients with advanced head and neck cancer].

BACKGROUND: Primary radiochemotherapy is gaining increasing importance for the treatment of advanced head and neck squamous cell carcinomas. However, there is a lack of clinical factors concerning prognostic information in relation to treatment. In this pilot study, we examined whether molecular factors can provide such information. PATIENTS AND METHODS: The expression patterns and their possible prognostic relevance of the cell cycle regulatory proteins p53, p21(WAF/CIP1), Rb, p16(INK4A), CDK4 and Cyclin D1, MIB1 (Ki-67) and BCL-2 were analysed in pretreatment tumor biopsies from 43 patients with advanced carcinomas of the oropharynx (n = 26), hypopharynx (n = 10) and larynx (n = 7) by applying immunohistochemistry to paraffin sections of tumor specimens. All patients were treated by the same method of an accelerated "concomitant boost" radiochemotherapy with carboplatin in a phase II study. Median followup time was 56 months. RESULTS: No correlation was found between any of the markers and the remission rate, T-stage, N-stage, rate of loco-regional recurrences and distant metastases. However, independent of the tumor stage, patients with CDK4/cyclin-D1 overexpressing tumors had a significantly shortened overall survival (P = 0.014 and 0.026, respectively). CONCLUSION: The results of this pilot study indicate that CDK4 and cyclin D1 over-expression provide useful prognostic information about clinical outcome after primary radiochemotherapy of head and neck cancer patients.

Adult↗
PubMed1999

Heparin-induced thrombocytopenia: clinical considerations of alternative anticoagulation with various glycosaminoglycans and thrombin inhibitors.

Heparin-induced thrombocytopenia (HIT), the most common complication of heparin therapy, is also the most common form of the drug-induced thrombocytopenias. HIT is classified as type I and type II, the first being benign and the latter severe. HIT type II is attributed to an immune response characterized by complexes of heparin and platelet factor (PF) 4. Enzyme-linked immunosorbent assays allow easy and simple determination of these antibody titers; however, because specificity and sensitivity is not optimal, there is concern that the clinical relevance may be low. In clinical trials many patients were shown to form HIT-IgG in response to heparin without developing manifestations of HIT type II. Therefore, routine screening of clinically asymptomatic patients for antiheparin/PF 4 antibodies is not recommended. HIT type II is a clinico-pathologic syndrome that ideally should be confirmed by laboratory testing. If any clinical suspicion arises, however, heparin and low molecular weight heparin therapy should be discontinued and an alternative anticoagulant therapy started. Alternative drugs have been evaluated in significant numbers of patients including danaparoid and thrombin inhibitors. In the case of danaparoid, it is highly recommended that an in vitro test for cross-reactivity be performed before the onset of therapy. If testing cannot be performed, immediate administration of a thrombin inhibitor is preferred.

Anticoagulants↗
PubMed1999

Soluble adhesion molecules in the HIT syndrome: pathophysiologic role and therapeutic modulation.

Heparin-induced thrombocytopenia pathophysiology is now known to be a complex process that involves platelets, vascular endothelium, and leukocytes/lymphocytes. The activation products from these sites also contribute to the activation of coagulation and fibrinolytic deficit. While many of the markers of hemostatic activation processes have been found to be increased during the acute phase of heparin-induced thrombocytopenia syndromes, the circulating levels of soluble adhesion molecules such as the P, E, and L selectins, and intracellular and vascular cell adhesion molecules have not been reported. Since the pathophysiology of heparin-induced thrombocytopenia involves the activation of platelets, endothelium, and leukocytes, it is expected that the activation products related to these hemostatic systems including soluble selectins and cellular adhesion molecules will also be increased in circulating blood. These alterations may also provide an index of the pathophysiologic process. With the availability of highly sensitive enzyme-linked immunosorbent assays for soluble P, E, and L selectins, intracellular and vascular cell adhesion molecules, it is now possible to measure these adhesion molecules in biological fluids. This study reports on the circulating levels of various adhesion molecules in patients with heparin-induced thrombocytopenia and their modulation after therapeutic interventions by the use of direct thrombin inhibitors. With the availability of recombinant hirudin, it is now possible to treat these patients with alternate antithrombin agents. However, the immunoactivation of platelets and other cells as shown here indicates the possible need for additional adjunct therapeutic approaches to suppress their participation in the thrombotic process. The reported increase in the circulating levels of the soluble adhesion molecules during the heparin-induced thrombocytopenia and heparin-induced thrombocytopenia with thrombosis syndrome suggests that the antiheparin platelet factor 4 antibody is capable of modulating their regulation. The prognostic role of these mediators in the management of heparin-induced thrombocytopenia syndrome warrants further investigation.

Antithrombins↗
PubMed1999

Heparin-induced thrombocytopenic potential of GAG and non-GAG-based antithrombotic agents.

We have undertaken these studies of the heparin-like, or glycosaminoglycan, and nonglycosaminoglycan-based antithrombotics in an effort to add to the understanding of the pathophysiologic mechanism of heparin-induced thrombocytopenia by investigations of how glycosaminoglycan-related agents interact with the heparin-induced thrombocytopenia antibodies. The low molecular weight heparins, originally thought to be useful alternatives to heparin because of their smaller size, show platelet activation and aggregation responses in platelet heparin-induced thrombocytopenia serum systems (P-selectin expression, microparticle formation, serotonin release, platelet aggregation). Although the molecular mass and sulfation of the heparinoid Lomoparan is similar to that of heparin and low molecular weight heparins, its chemical structure is different and probably is not recognized by the heparin-induced thrombocytopenia antibodies. The heparin-related pentasaccharide did not show a positive reaction in any system of platelet activation/aggregation. These studies have shown that the antibodies produced in patients with heparin-induced thrombocytopenia are reactive to highly sulfated glycosaminoglycans and nonglycosaminoglycan agents and less dependent on the molecular mass of these agents; whether the agent is a heparin or nonheparin compound was not critical. A combination of a moderate sulfation but low molecular mass in a heparin-like molecule was sufficient to prevent interaction with the heparin-induced thrombocytopenia antibodies. However, a chemical structure that is different from heparin (e.g., a heparinoid or a thrombin inhibitor) will also be nonreactive to platelet activation by heparin-induced thrombocytopenia antibodies.

Antibodies↗
PubMed1999

[Hyperthyroidism and acute renal failure in partial bladder mole].

We report on a 31-year-old II gravida I para treated because of a hydatidiform mole, hyperthyroidism and acute renal failure in the 16th week of pregnancy. The pathomechanism of trophoblast-induced hyperthyroidism will be discussed. To our knowledge this is the first report on acute renal failure in association with trophoblast-induced hyperthyroidism.

Abortion, Eugenic↗
PubMed1999

First workshop for detection of heparin-induced antibodies: validation of the heparin-induced platelet-activation test (HIPA) in comparison with a PF4/heparin ELISA.

BACKGROUND: No data exist regarding the inter-laboratory reproducibility of the heparin-induced-platelet-activation (HIPA) test, the most widely used functional assay in Germany for the detection of heparin-induced thrombocytopenia (HIT) antibodies. METHODS: Nine laboratories used an identical protocol to test eight different sera with the HIPA test. Five laboratories also tested the sera with a platelet factor 4 (PF4)/heparin-complex ELISA. Cross-reactivity with danaparoid-sodium was assessed using 0.2 aFXa units instead of heparin in the HIPA test. RESULTS: Two of nine laboratories had no discrepant HIPA test results. Four laboratories differed in one sample, one reported two discrepant results, and two laboratories reported more than two discrepant results. Cross-reactivity with danaparoid-sodium test results differed among laboratories. PF4/heparin ELISA results were identical in all five laboratories. CONCLUSION: The HIPA test requires strict quality control measures. Using both a sensitive functional assay (HIPA test) and a PF4/heparin ELISA will allow detection of antibodies directed to antigens other than PF4/heparin complexes as well as detection of IgM and IgA antibodies with PF4/heparin specificity.

Antibodies↗
PubMed1999

Selectins in the HIT syndrome: pathophysiologic role and therapeutic modulation.

The pathophysiology of heparin-induced thrombocytopenia (HIT) is now known to be a complex process which involves platelets, vascular endothelium, and leukocytes. The activation products from these sites also contribute to the activation of coagulation and to the fibrinolytic deficit. While many of the markers of hemostatic activation processes have been found to be at increased levels during acute phases of the HIT syndromes, the circulating levels of soluble P-, E-, and L- selectins have not been reported. Since the pathophysiology of HIT involves the activation of platelets, endothelium, and leukocytes, it is expected that activation products related to these hemostatic systems, including soluble selectins, will also be increased in circulating blood. These alterations may provide an index of the pathophysiologic process. With the availability of highly sensitive ELISAs for soluble P-, E-, and L-selectins, it is now possible to measure these adhesion molecules in biological fluids. This study reports on the circulating levels of P-, E-, and L-selectins in HIT patients and their modulation after therapeutic intervention. With the availability of recombinant hirudin, it is now possible to provide alternate anticoagulants to HIT patients. However, the immunoactivation of platelets and other cells may require additional adjunct therapeutic approaches.

Anticoagulants↗
PubMed1999

Heparin-induced thrombocytopenia: the role of platelet activation and therapeutic implications.

In the past, heparin has been the sole anticoagulant for interventional cardiovascular procedures. Today, several alternate approaches to anticoagulate patients with heparin-induced thrombocytopenia (HIT) are under consideration. Antiplatelet drugs, such as the ADP receptor antagonists and inhibitors of glycoprotein (GP) IIb/IIIa, are currently in development. We investigated the effect of two anti-platelet agents on platelet activation induced by HIT serum (n = 5 HIT positive sera, n = 5 HIT negative sera and n = 4 donor platelets) and heparin, using the traditional platelet aggregation assay, a Lumi-aggregation assay to also determine platelet release, and flow cytometry. By all methods, the GP IIb/IIIa inhibitor-GPI 562 (Novartis; Nürnberg, Germany)-produced a concentration dependent (6.25 to 125 ng/mL) decrease in platelet activation, as shown by platelet aggregation, platelet microparticle formation, P-selectin expression, and ATP release. Similar results were obtained with the thienopyridine ADP receptor antagonist ticlopidine (Sanofi Recherche; Toulouse, France) in vitro at high concentrations of 5.0 to 50 microg/mL and ex vivo in a patient dosed at 250 mg/day. These studies show that GP IIb/IIIa and ADP receptor inhibitors can block platelet activation induced by HIT serum/heparin, providing evidence that the mechanism of HIT may be multifactorial involving not only the generation of the heparin-PF4 or other antibodies but also involving platelet-specific processes and, potentially, the generation of proaggregatory substances. The new antiplatelet agents may be useful in the clinical management of HIT patients.

Adenosine Triphosphate↗