Room temperature and low-field resonant enhancement of spin Seebeck effect in partially compensated magnets.

Resonant enhancement of spin Seebeck effect (SSE) due to phonons was recently discovered in Y[Formula: see text]Fe[Formula: see text]O[Formula: see text] (YIG). This effect is explained by hybridization between the magnon and phonon dispersions. However, this effect was observed at low temperatures and high magnetic fields, limiting the scope for applications. Here we report observation of phonon-resonant enhancement of SSE at room temperature and low magnetic field. We observe in Lu[Formula: see text]BiFe[Formula: see text]GaO[Formula: see text] an enhancement 700% greater than that in a YIG film and at very low magnetic fields around 10[Formula: see text] T, almost one order of magnitude lower than that of YIG. The result can be explained by the change in the magnon dispersion induced by magnetic compensation due to the presence of non-magnetic ion substitutions. Our study provides a way to tune the magnon response in a crystal by chemical doping, with potential applications for spintronic devices.

HIV-HCV co-infected patients with low CD4+ cell nadirs are at risk for faster fibrosis progression and portal hypertension.

Patients co-infected with the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) are fraught with a rapid fibrosis progression rate and with complications of portal hypertension (PHT) We aimed to assess the influence of immune function [Centers of Disease Control and Prevention (CDC) stage] on development of PHT and disease progression in HIV-HCV co-infection. Data of 74 interferon-naïve HIV-HCV co-infected patients undergoing liver biopsy, measurement of portal pressure and of liver stiffness and routine laboratory tests (including CD4+ cell count, HIV and HCV viral load) were analysed. Time of initial exposure (risk behaviour) was used to assess fibrosis progression. Fibrosis progression, time to cirrhosis and portal pressure were correlated with HIV status (CDC stage). HIV-HCV patients had rapid progression of fibrosis [0.201 +/- 0.088 METAVIR fibrosis units/year (FU/y)] and accelerated time to cirrhosis (24 +/- 13 years), high HCV viral loads (4.83 x 10(6) IU/mL) and a mean HVPG at the upper limit of normal (5 mmHg). With moderate or severe immunodeficiency, fibrosis progression was even higher (CDC-2 = 0.177 FU/y; CDC-3 = 0.248 FU/y) compared with patients with higher CD4+ nadirs (CDC-1 = 0.120 FU/y; P = 0.0001). An indirect correlation between CD4+ cell count and rate of fibrosis progression (R = -0.6654; P < 0.001) could be demonstrated. Hepatic venous pressure gradient (HVPG) showed early elevation of portal pressure with median values of 4, 8 and 12 mmHg after 10, 15 and 20 years of HCV infection for CDC-3 patients. Patients treated with highly active anti-retroviral therapy (HAART) had similar rates of progression and portal pressure values than patients without HAART. Progression of HCV disease is accelerated in HIV-HCV co-infection, being more pronounced in patients with low CD4+ cell count. A history of a CD4+ cell nadir <200/microL is a risk factor for rapid development of cirrhosis and PHT. Thus, HCV treatment should be considered early in patients with HIV-HCV co-infection and largely preserved CD4+ cell counts.

Suppression of haematopoiesis during therapy of chronic hepatitis C with different interferon alpha mono and combination therapy regimens.

BACKGROUND: Treatment of chronic hepatitis C with interferon (IFN)-alpha and ribavirin has haematotoxic effects. We evaluated the effects of four different IFN/IFN-ribavirin treatment regimens on haematopoiesis. METHODS: Haematopoiesis was studied in 133 patients with chronic hepatitis C receiving IFN-alpha2b alone (group A) or in combination with ribavirin (group B), pegylated IFN-alpha2a (group C), or pegylated IFN-alpha2b (group D) in combination with ribavirin. RESULTS: At week 4, haemoglobin levels were diminished in all groups receiving combination therapy. In the monotherapy group, haemoglobin decreased slightly after eight weeks. In all groups, haemoglobin remained diminished throughout therapy. In all patients, leucocytes (while blood cells) decreased after four weeks and remained low during treatment. Platelets (peripheral platelet count (PPC)) were decreased in all groups after four weeks and remained below baseline levels during therapy in group A, C, and D whereas in group B PPC recovered early and reached baseline levels at week 16 of therapy. Concomitantly with the decreases in haemoglobin and PPC, erythropoietin increased in all groups receiving combination therapy and thrombopoietin in all groups. Patients treated with pegylated IFN-alpha2a and those who received pegylated IFN-alpha2b combination therapy differed only in leucopoiesis, whereas erythropoiesis and thrombopoiesis were comparable. CONCLUSION: IFN-alpha based therapies are associated with a decrease in all three haematopoietic lineages, irrespective of the type of therapy used. The stronger suppressive effect of pegylated IFN-alpha2a on leucopoiesis could be due to a dose effect. Overall, concentrations of endogenous haematopoietic growth factors are increased but can only partially alleviate haematotoxicity. Potential uses of exogenous haematopoietic growth factors and their impact on the virological response need to be explored.

Bradycardia and sinus arrest during percutaneous ethanol injection therapy for hepatocellular carcinoma.

BACKGROUND: Percutaneous ethanol injection (PEI) is an established method in the treatment of hepatocellular carcinoma (HCC) and considered a safe procedure, with severe complications occurring rarely. Cardiac arrhythmias have not been reported to date. Aim of the study was to investigate the occurrence of dysrhythmias during PEI. PATIENTS AND METHODS: Twenty-six consecutive patients with inoperable HCC were included. During ultrasound-guided PEI with 95% ethanol, electrocardiogram (ECG) monitoring was performed before starting and continuously during PEI. RESULTS: During PEI a significant reduction in mean heart rate (> 20%) was seen in 15 of 26 (58%) patients. In 11 of 26 patients (42%) occurrence of sinuatrial block (SAB) or atrioventricular block (AVB) was observed after a median time of 9 s (range 4-50) from the start of PEI with a median length of 24 s (range 12-480). Clinical symptoms were seen in two patients, including episodes of unconsciousness, seizure-like symptoms in both and a respiratory arrest during PEI in one patient, requiring mechanical ventilation. In four of 12 patients with repeat interventions, dysrhythmias were reproducible during monthly performed procedures. There was a significant association between the occurrence of SAB or AVB and the amount of instilled alcohol (P = 0.03) and post-PEI serum ethanol levels (P = 0.03). CONCLUSIONS: Bradycardia and block formation occur frequently during PEI. These symptoms could be explained by a vasovagal reaction and/or the direct effect of ethanol on the sinus node or the right atrial conduction system. Ethanol dose is an important factor for the occurrence of SAB/AVB. ECG-monitoring seems mandatory during PEI. Prophylactic use of intravenously administered Atropine might be useful.

Child-Pugh versus MELD score in predicting survival in patients undergoing transjugular intrahepatic portosystemic shunt.

BACKGROUND: In patients undergoing transjugular intrahepatic portosystemic shunt (TIPS), prognostic scores may identify those with a poor prognosis or even those with a clear survival benefit. The Child-Pugh score (CPS) is well established but several drawbacks have led to development of the model of end stage liver disease (MELD). AIM: The aim of the study was to compare the predictive power of CPS and MELD, to validate the original MELD formula, and to assess the predictive value of the determinants used in the two prognostic scores outside of a study setting. PATIENTS: A total of 501 patients underwent elective TIPS placement and 475 patients fulfilled the inclusion criteria. METHODS: Data of all patients undergoing elective TIPS in one university hospital and four community hospitals in Vienna, Austria, between 1991 and 2001, were analysed retrospectively. The main statistical tests were Cox proportional hazards regression model, the log rank test, Kaplan-Meier analysis, and concordance c statistics. RESULTS: Median follow up was 5.2 years and median survival was 4.6 years. During follow up, 230 patients died, 75 within three months after TIPS placement. In stepwise proportional hazards analyses, independent predictors of death were creatinine level, bilirubin level, age, and refractory ascites. MELD was better in predicting survival in a stepwise Cox model but both scores were equally predictive in c statistics for one month, three month, and one year survival. Renal function was the strongest independent predictor of survival. CONCLUSIONS: Although MELD was the primary predictor of overall survival in multivariate analysis, c statistics showed that both scores can be used for patients undergoing TIPS with equal accuracy. For assessing prognosis in patients undergoing TIPS implantation, there seems little reason to replace the well established Child-Pugh score.

Characterization of (123)I-vascular endothelial growth factor-binding sites expressed on human tumour cells: possible implication for tumour scintigraphy.

To explore the possibility of vascular endothelial growth factor (VEGF) receptor scintigraphy of primary tumours and their metastases, we analysed the binding properties of (123)I-labelled VEGF(165) ((123)I-VEGF(165)) and (123)I-VEGF(121) to human umbilical vein endothelial cells (HUVECs), several human tumour cell lines (HMC-1, A431, KU812, U937, HEP-1, HEP-G2, HEP-3B and Raji), a variety of primary human tumours (n = 40) and some adjacent non-neoplastic tissues as well as normal human peripheral blood cells in vitro. Two classes of high-affinity (123)I-VEGF(165)-binding site were found on the cell surface of HUVECs. In contrast, one class of high-affinity binding sites for (123)I-VEGF(165) was found on HMC-1, A431, HEP-1, HEP-G2, HEP-3B and U937 cells as well as many primary tumours. For (123)I-VEGF(121), a single class of high-affinity binding site was found on certain cell lines (HUVEC, HEP-1 and HMC-1) and distinct primary tumours (primary melanomas, ductal breast cancers and ovarian carcinomas as well as meningiomas). Tumour cells expressed significantly higher numbers of VEGF receptors compared with normal peripheral blood cells and adjacent non-neoplastic tissues. Immunohistochemical staining revealed that the VEGF receptor Flk-1 is expressed to a much higher extent within malignant tissues compared with neighbouring non-neoplastic cells. We observed significantly greater specific binding of (123)I-VEGF(165) and (123)I-VEGF(121) to a variety of human tumour cells/tissues compared with the corresponding normal tissues or normal peripheral blood cells. In comparison with (123)I-VEGF(121), (123)I-VEGF(165) bound to a higher number of different tumour cell types with a higher capacity. Thus, (123)I-VEGF(165) may be a potentially useful tracer for in vivo imaging of solid tumours.

Thrombopoietin in Plasmodium falciparum malaria.

Thrombopoietin (TPO) is the key growth factor for platelet production and is elevated in states of platelet depletion. As thrombocytopenia is a common finding in malaria, we analysed TPO regulation before, during and after antimalarial treatment. Before treatment, TPO serum levels were significantly higher in patients with severe malaria (n = 35) than in patients with uncomplicated malaria (n = 44; P = 0.024), normalizing within 14-21 d of therapy. The rapid normalization of TPO levels and increase in low peripheral platelet counts after treatment indicate that the biosynthesis of TPO and its regulation in malaria patients are normal.

Thrombopoietin induces rapid resolution of thrombocytopenia after orthotopic liver transplantation through increased platelet production.

Thrombopoietin (TPO) deficiency has been proposed as an important etiologic factor for thrombocytopenia in advanced-stage liver disease. To clarify the contributions of platelet production, platelet consumption, coagulation activation, and splenic sequestration to thrombocytopenia in liver disease, we studied TPO serum levels and markers of platelet production, platelet activation, and coagulation activation before and 14 days after orthotopic liver transplantation (OLT) in 18 patients with advanced liver cirrhosis. Thrombocytopenia before transplantation occurred with low-normal serum levels of TPO, normal levels of platelet and coagulation activation markers, and no increase in bone marrow production of platelets. TPO serum levels increased significantly on the first day after OLT, preceding the increase of reticulated platelets by 3 days and peripheral platelets by 5 days. Normalization of the peripheral platelet count occurred in most patients within 14 days of OLT, irrespective of the change in spleen size assessed by computed tomography volumetry. Normalization of platelet counts was not hampered by a certain degree of platelet activation observed during the steepest increase in the peripheral platelet count. Bone marrow production of platelets increased significantly within 2 weeks of transplantation. Low TPO serum levels with low platelet counts and without platelet consumption suggests low TPO production in end-stage liver disease. The rapid increase in TPO serum levels after transplantation induces an increase in the bone marrow production of platelets. Decreased TPO production in the cirrhotic liver is an important etiologic factor for thrombocytopenia in liver disease that is rapidly reversed by transplantation.

[In vitro evaluation of potentially effective gemcitabine combination therapy for exocrine pancreatic carcinoma]. / In-vitro-Evaluierung potentiell effektiver Gemcitabine-Kombinationstherapien beim exokrinen Pankreaskarzinom.

The aim of the present study was to define potentially synergistic gemcitabine drug combinations for the treatment of pancreatic adenocarcinoma by using a tumour-specific in vitro screening system. The anticancer drug screening system used for these experiments consisted of four different established human pancreatic adenocarcinoma cell lines (BxPc-3, Panc-1, ASPC-1, Ca-pan-1) and the Microculture Tetrazolium (MTT) Assay for quantification of cytotoxic drug effects. To define single agent activities, dose-response curves, IC 50 values, and in order to validate the test system, in a first step gemcitabine and several conventional anticancer drugs including 5-FU, cisplatin, epirubicin, and mitomycin C were tested at 10 different concentrations ranging from 0.001 to 100 micrograms/ml. The effectiveness of various gemcitabine combinations was subsequently determined by using clinically relevant in vitro drug concentrations, and was rated as synergistic, additive or subadditive according to the criteria of Aapro. Overall, a heterogeneous chemosensitivity pattern was noted within the four tested cell lines. In agreement with the known chemotherapeutic refractoriness of pancreatic cancer, major cytotoxic effects were only seen with use of rather high drug concentrations. Investigation of various drug exposure times revealed a superior antiproliferative activity of gemcitabine and the other compounds in case of prolonged incubation. During subsequent drug combination experiments, gemcitabine + cisplatin and gemcitabine + epirubicin resulted in synergistic activity in 2/4 cell lines each. As opposed to the poor activity of single agents, a > 50% growth inhibition (in vitro response) was noted in 3 and 2 cell lines, respectively. Experimental data obtained with this pancreatic cancer specific in vitro screening system suggest that dose escalation or prolonged administration of gemcitabine, as well as the combination of this drug with cisplatin or epirubicin might result in improved therapeutic results. Encouraging preliminary results obtained in phase II studies seem to support the potential clinical relevance of the described disease-oriented screening system.