Picosecond optical switching based on biphotonic excitation of an electron donor-acceptor-donor molecule.

An electron donor-acceptor-donor molecule consisting of two porphyrin donors rigidly attached to the two-electron acceptor N,N'-diphenyl-3,4,9,10-perylenebis(dicarboximide) acts as a light intensity-dependent molecular switch on a picosecond time scale. Excitation of the porphyrins within this molecule with subpicosecond laser pulses results in single or double reduction of the acceptor depending on the light intensity. The singly and doubly reduced electron acceptors absorb light strongly at 713 and 546 nanometers, respectively. Because these absorption changes are produced solely by electron transfers, this molecular switch effectively has no moving parts and switches significantly faster than photochromic molecules that must undergo changes in molecular structure.

Carbohydrate Antigen 19-9 Level in Patients with Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent monogenic renal disease, responsible for 10% of the patients on renal replacement therapy, including kidney transplantation. Recently, it was reported that the serum CA 19-9 level is significantly elevated in ADPKD patients without malignancy. Exclusion of malignancy, including tumor marker analysis, is essential in pretransplant evaluation, as well as in assessment of kidney transplantation recipients. METHODS: In this study the serum CA 19-9 level in ADPKD patients without malignancy was retrospectively analyzed. The mean level of CA 19-9 was 30.3 U/mL (0.8 U/L-612 U/L). RESULTS: Overall, in 24 patients (18.8%) the serum CA 19-9 level was increased above the normal level found in the general population (35 U/L), and 5 of them (4.2%) did not experience polycystic liver disease. In 4 patients (3.4%) CA 19-9 level was increased 2-fold above the norm and in 3 of them (2.5%) 3-fold over the norm and higher. A statistically significant negative correlation between serum CA 19-9 level and estimated glomerular filtration rate, both in patients with and without hepatic cysts was observed. In nearly 1 in 5 patients with ADPKD, serum CA 19-9 level should be expected to be above the norm found in the general population, despite the lack of coexistence of a tumor or cholangitis. CONCLUSION: This finding should be considered during transplantation qualification and in follow-up examination after kidney transplantation.

Results of a 6-month, multicenter, open-label, prospective study concerning efficacy and safety of mycophenolate sodium in de novo kidney transplant recipients.

BACKGROUND: Mycophenolate sodium (MPS) was designed to reduce the gastrointestinal side effects of mycophenolic acid. The aim of our study was to determine the safety and efficacy of MPS in de novo renal transplant recipients. PATIENTS AND METHODS: This 6-month, multicenter, open-label, single-arm, prospective study was carried out in three centers in Poland. Thirty patients were recruited. Immunosuppressive regimen contained of MPS and cyclosporine (CsA) with or without steroids. RESULTS: The 6-month graft and patient survival was 100%. The incidence of suspected acute rejection episodes (ARE) was 5/30 (16.7%), including biopsy-proven ARE in 2 (6.7%) cases. ARE reversed after therapy. At month 6, the mean serum creatinine level was 1.4 mg/dL, and the mean creatinine clearance (according to the Cockroft-Gault formula) was >70 mL/min. The most frequent adverse effects included diarrhea, delayed graft function, anemia, and lymphocele. Among infections, most common were infections of urinary tract, cytomegalovirus infections, and infections of respiratory tract. Only three patients (10.0%) terminated the study prematurely, including two who discontinuated because of an adverse event, and one because of noncompliance. CONCLUSIONS: An immunosuppressive regimen, including MPS and CsA, with or without steroids, provided effective antirejecton prophylaxis and was well tolerated.

The influence of immuosuppressive therapy on the development of CD4+CD25+ T cells after renal transplantation.

A growing number of studies suggest that CD4(+)CD25(+) T regulatory (Treg) cells play a significant role to downregulate the immune response to alloantigens. In this study, we investigated the possible influence of immunosuppressive therapy, including cyclosporine (CsA) or rapamycin (sirolimus), on the level of CD4(+)CD25(+), CD4(+)CD25(+)FOXP3(+), and CD4(+)CD25(+)CTLA-4(+) T cells in the peripheral blood of renal allograft recipients. The study was performed on renal allograft recipients who displayed uneventful stable courses (RAR-S; n = 15) versus biopsy-proven chronic rejection (RAR-CH; n = 12). The patients were divided based on the immunosuppressive protocol: group 1 (prednisone+CsA+Aza) and group II (prednisone+sirolimus). The control group consisted of 10 healthy blood donors. We examined the expression of CD4, CD25, CTLA-4, and Foxp3 in peripheral blood T cells. Flow cytometry was performed with a FACSCalibur (BD Biosciences) instrument with data analyzed using Cell Quest software. The percentage of CD4(+)CD25(+)Foxp3(+) T cells in rapamycin (sirolimus) treated patients did not differ from that observed in healthy individuals, but was significantly higher compared with CsA-treated patients. CsA therapy resulted in a reduction in the percentage of CD4(+)CD25(+)CTLA-4(+) and CD4(+)CD25(+)Foxp3(+) regulatory T cells after renal transplantation in both groups (RAR-S and RAR-CH) compared with patients treated with rapamycin or to healthy donors. The type of immunosuppressive therapy (with or without calcineurin inhibitors) may have an important role in tolerance induction and graft function.

Economic evaluation of sirolimus-based immunosuppressive regimens in kidney graft recipients.

INTRODUCTION: The aim of this study was an economic evaluation of three sirolimus (SRL)-based regimens in the first 2 years after renal transplantation. MATERIALS AND METHODS: The three SRL-based immunosuppressive regimens in renal transplant patients between June 2000 and September 2002 were: (1) SRL + steroids + cyclosporine (CsA) permanently; (2) SRL + steroids + tacrolimus (Tac); and (3) SRL + steroids + CsA, with CsA discontinuation at 3 months posttransplant. Ten patients were included in each group in an intent-to-treat analysis. Cost was calculated according to the hospital price list and recast into euros (EUR) with a 5% discount rate. RESULTS: The number of patients free of an acute rejection episode during 2 years posttransplant were 6, 8, and 5, with 2-year graft and patient survivals of 9, 10, and 9 for regimens 1, 2, and 3, respectively. As differences in clinical effects were not statistically significant, cost analysis was appropriate instead of cost-effectiveness analysis. The mean cost of the 2-year treatment was 15,759 EUR; 25,593 EUR; and 21,197 EUR per patient for regimens 1, 2, and 3, respectively. Sensitivity analysis for the main variables confirmed that the results were not dependent on changes in costs. CONCLUSIONS: Regimen 1 was the most economical immunosuppressive therapy during the 2 years after kidney transplantation. Studies on a larger group of longer observation would be more useful for clinical analysis.

[Simultaneous use of different nuclear medical examinations in Klippel-Trenaunay syndrome--vs. Proteus syndrome]. / Simultaner Einsatz verschiedener nuklearmedizinischer Verfahren bei Klippel-Trenaunay-Syndrom--vs. Proteus-Syndrom.

A three-year-old male patient presented already at his birth a disproportion macrosomia of the left foot and a large, nodular nevus flammeus in the left hip region, which led to the tentative diagnosis of a Klippel-Trenaunay syndrome. In the following years, both changes showed a continuous progression, with distinct soft-tissue swelling as well as papillomatous and verruciform vegetations of the nevus. Additionally, large, plain subcutaneous masses developed under the right shoulder, and a macrodactyly of the first and second left toe could be observed. Although several examinations had been performed in the meantime, the tentative diagnosis could not be confirmed up to that time. On the occasion of a severe local infection in the hip region, which led to the consideration of a surgical therapy, a radionuclide lymphography, a blood pool scintigraphy including dynamic phlebography and ventriculography as well as a bone scintigraphy were performed. These examinations were done simultaneously at one day in order to avoid a longer period of immobilization. The findings led to the diagnosis of a large lymphangioma, which could be confirmed histologically after surgery. In consideration of all results, the basic disorder seems to be the rare proteus syndrome rather than a Klippel-Trenaunay syndrome.

Liver transplantation in hepatitis C virus-related cirrhosis.

End-stage liver disease associated with HCV infection has become one of the leading indications for liver transplantation and it is the most common disease recurring after liver transplantation. The aim of this retrospective study was to asses factors potentially affecting outcome in patients transplanted for HCV-related liver disease. Among 164 adult patients who underwent orthotopic liver transplantation from December 1994 to December 2002, 134 survived >2 months, including 25 with HCV-related liver disease. Mean follow-up after LTx was 24.8 months (range, 2.1-99.4). Anti-HCV was negative in all donors. The parameters considered in our analysis were: the course, outcome, and liver function tests at 1-year follow-up after HCV reinfection: the potential impact of maintenance and induction immunosuppressive regimens; and episodes of acute rejection. Deterioration of graft function because of HCV reinfection occurred in 16 patients (64%). Mean time for deterioration of liver function related to reinfection was 4.5 months (range, 0.83-23). Induction and maintenance immunosuppression did not affect outcome of HCV-infected liver transplant recipients. Aminotransferases were significantly higher among HCV-infected recipients than among the other patients in our series. There was a slight tendency for earlier recurrence of HCV hepatitis among patients treated with high-dose steroids because of acute rejection.

[A method of averaged ECG signal does not identify patients with ventricular tachycardia in disorders of intraventricular conduction]. / Technika usredniania sygnalu EKG nie pozwala na wyodrebnienie chorych z czestoskurczem komorowym przy zaburzeniach przewodnictwa sródkomorowego.

Conduction defect are known to delay and fragment the ecg signal and may be expected to cause changes on the signal-averaged ecg that mimic ventricular late potentials. The aim of our study was to asses whether signal-averaged ECG (SAE) identify patients (pts) with sustained ventricular tachycardia (VT) after myocardial infarction (MI) who display right or left bundle branch block (RBBB or LBBB). We studied 23 pts with RBBB and 25 pts with LBBB. SEA was recorded with bidirectional filters at 25-250 HZ and 40-250 Hz using Simson method. The total filtered QRS duration (QRSd), root mean square voltage in the terminal 40ms of the QRS (RMS40) and low amplitude signal duration less than 40uV (LAS40)) were measured. Signal-averaged parameters with a filter at 25-250 Hz were: [table: see text] Signal-averaged parameters with a filter at 40-259 Hz were: [table: see text] In conclusion SAE parameters do not allow separation of pts with sustained VT from pts with RBBB or LBBB after MI. These data indicate that conduction defects have effects on signal-averaged ecg parameters and may result in masking of ventricular late potentials.

Intracranial aneurysms in autosomal dominant polycystic kidney disease.

BACKGROUND AND PURPOSE: ADPKD correlates with an increased frequency of ICANs, but universal screening for ICANs in patients with ADPKD is not currently recommended. The aim of our study was to determine which groups might benefit from screening by determining the prevalence of ICANs in the Polish ADPKD population and identifying any subgroups with an increased risk for ICANs. MATERIALS AND METHODS: Eighty-three adult, predialysis-phase patients with ADPKD underwent screening for ICANs with MRA of the brain. RESULTS: The prevalence of ICANs in the studied population was 16.9%, with 6% of the screened group requiring neurosurgical intervention. We also found that the frequency of ICANs increases with age, reaching 22.4% in patients older than 45 years. All diagnosed ICANs were small (< 9 mm) and were localized in the anterior circulation. In addition, MR imaging revealed arachnoid cysts in 4.8% of patients with ADPKD. CONCLUSIONS: We suggest that patients older than 45 years with ADPKD be considered as candidates for screening for ICANs, and we propose a clinical algorithm for this subgroup. However, we could not find risk factors for ICANs in younger patients with ADPKD.

Human peripheral blood CD8+ CD28- T cells of renal allograft recipients do not express FOXP3 protein.

INTRODUCTION: In recent studies, the FOXP3 molecule has been suggested to be a marker of a suppressor subset of human CD8+ CD28- T cells based on correlations between the level of its mRNA and allograft function. Because this transcriptional factor produces a protein, we suggest that these correlations should focus on the FOXP3 protein. The aim of our study was to evaluate whether FOXP3 protein was present in cells of the CD8+ CD28- population in the peripheral blood of renal allograft recipients and whether the level of CD8+ CD28- FOXP3+ cells correlated with allograft function. METHODS: The study was performed on 30 renal allograft recipients with uneventful stable courses (n=18) or biopsy-proven chronic rejection (n=12). The immunosuppression was based on cyclosporine (n=12) or rapamycin (n=9). Peripheral blood mononuclear cells isolated from recipient blood samples were labeled with anti-CD8 and anti-CD28 MAbs conjugated with fluorochromes. After incubation, washing, and labeling using a PE anti-human FOXP3 Kit, we determined the percentage of cells by flow cytometry. RESULTS: FOXP3 protein expression was not observed either in the CD8+ CD28- population, or the whole populations of CD8+ or CD28- cells among patient groups. CONCLUSIONS: The expression of FOXP3 protein in CD8+ CD28- cells seems to be of a questionable value as a diagnostic tool for allograft function, it is probably not a marker for the CD8+ CD28- T cell subset.

Intestine as source of cytokines and growth factors.

BACKGROUND: The activation status of intestinal immune system cells is much higher than that of analogous peripheral cells. Increased serum concentrations of proinflammatory cytokines have been reported in various pathologic conditions; however, the source of these mediators has not been elucidated. OBJECTIVE: To assess the role of the human intestine and its lymphatic system in production of growth factors and proinflammatory cytokines. MATERIAL AND METHODS: Twenty liver transplant recipients and 20 donors were included in the study. Blood samples were obtained from the artery supplying the intestine, the portal vein, and a peripheral vein during liver harvesting in donors and after transplantation in recipients. An enzyme-linked immunosorbent assay was used to assess serum concentrations of IL-6, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and hepatocyte growth factor (HGF). RESULTS: In transplant recipients, IL-6 concentration in arterial blood was lower than that in portal blood (P < .049), whereas in donors, there was no significant difference in these concentrations. Neither recipients nor donors demonstrated significant differences in arterial or portal blood concentrations of TNF-alpha, TGF-beta, or HGF. CONCLUSIONS: In healthy human beings, the intestine is not a substantial source of IL-6, TNF-alpha, TGF-beta, or HGF. However, in patients with liver cirrhosis, the intestine is an important source of IL-6 but not of the other studied growth factors and cytokines.

Characterization of cardiovascular events mediated by platelet activating factor during systemic anaphylaxis.

Previous studies have shown that an anaphylactic reaction in the isolated perfused heart is characterized by drastic coronary constriction, arrhythmias, and severe impairment of contractility. In vivo anaphylaxis is associated with myocardial ischemia and rapid cardiovascular failure. Recently, not only histamine but also platelet activating factor (PAF) has been implicated in cardiac manifestation of anaphylaxis. The present study was designed to separate the effects of PAF from those of histamine on cardiovascular function during systemic anaphylaxis. In guinea pigs, sensitization was produced by subcutaneous (s.c.) application of ovalbumin. Fourteen days after sensitization, the effects of an intravenous (i.v.) infusion of ovalbumin were tested in anesthetized artificially ventilated guinea pigs. The renewed application of the antigen induced severe cardiac dysfunction. Within 3 min, cardiac output (CO) had already decreased by 90% and left ventricular end-diastolic pressure (LVEDP) increased significantly, indicating left ventricular pump failure. Concurrently, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, arrhythmias occurred in terms of atrioventricular block. After 4 min, blood pressure (BP) rapidly decreased. All animals died within 10 min. Pretreatment with the H1-receptor antagonist mepyramine (1 mg/kg i.v.) in combination with the H2-receptor antagonist cimetidine (10 mg/kg i.v.) delayed onset of myocardial ischemia, arrhythmias and cardiac pump failure. After 10 min, however, LV contractility and BP steadily decreased, leading to severe hypotension within 30 min. If the selective PAF antagonist WEB 2086 (1 mg/kg i.v.) was administered in addition to cimetidine and mepyramine, myocardial ischemia and LV contractile failure were markedly inhibited further. In contrast, pretreatment with WEB 2086 alone had no beneficial effects on the anaphylactic cardiovascular changes. Therefore, we conclude that histamine is the predominant mediator during the early phase of systemic anaphylaxis whereas PAF-mediated effects are involved in cardiac dysfunction during the protracted late phase of anaphylaxis.

[Prognostic value of an early peak CK-MB in plasma of patients treated with streptokinase for acute myocardial infarction]. / Wartosc prognostyczna wczesnego szczytu aktywnosci CK-MB w surowicy u chorych leczonych streptokinaza w ostrym zawale serca.

111 patients below 70 years old, with the first acute myocardial infarctions, 6 hours since the pain occurred--have been treated with streptokinase i.v. In 102 patients we obtained full curve of CK-MB activity. Early peak of CK-MB activity < 15 hours after onset of symptoms we have observed in 59 patients, and late peak of CK-MB activity > 15 hours in 43 patients. There was not any significant statistics differences between early and late groups in frequency of: early ventricular fibrillation (< 48 hours), complex ventricular arrhythmia (in 21 day), heart failure and in-hospital mortality. 1 patient died in hospital in early group and in late group also died 1 patient. The follow-up period was from 10 to 48 months (av. 26 +/- 13). 100 patients left the hospital and the full informations we have obtained in 97 cases. No one died in that time. In the group with early peak CK-MB activity we observed more often the unstable angina and the new myocardial infarction (21%) than in the group with late peak of CK-MB activity (15%), but these differences were nonsignificant. In conclusion our results don't confirm that the early peak of CK-MB activity is the positive risk factor of unstable angina and the new myocardial infarction.

Effects of platelet-activating factor on myocardial contraction and myocardial relaxation of isolated perfused guinea pig hearts.

Platelet-activating factor (PAF) is an important mediator of cardiovascular shock owing to immunologic reactions, including anaphylaxis and endotoxaemia. Previous studies have shown that PAF is a potent cardio-depressive agent causing a marked coronary constriction and a sustained impairment of myocardial contractility. In this study, we attempted to characterize further the prolonged PAF effects on coronary circulation and myocardial contractile force in isolated guinea pig hearts perfused at constant pressure (60 cm H2O) or constant flow which was adjusted to a level of 100% above basal flow. In addition, the PAF-induced changes of ventricular systolic and diastolic function were distinguished. In the hearts perfused at constant pressure, PAF induced a dose-dependent (0.57, 5.7, and 57 pmol/min) decrease of coronary flow rates, left ventricular pressure (LVP), LV contraction (peak positive dP/dt) and LV relaxation (peak negative dP/dt). The decrement of peak negative dP/dt was more pronounced than that of peak positive dP/dt. Maintenance of coronary flow rates only attenuated, but did not suppress, the PAF-induced ventricular malfunction, and it improved ventricular relaxation less than it did ventricular contraction. Pretreatment with the PAF antagonist WEB 2086 (19.7 nmol/min) almost completely abolished the effects of the highest PAF dose on coronary circulation and ventricular contractile parameters. We conclude that the cardiodepressive effects of PAF are due to coronary constriction and direct contractile events. Furthermore, PAF impairs ventricular diastolic function more than ventricular systolic function.

Effects of platelet-activating factor on beta- and H2-receptor-mediated increase of myocardial contractile force in isolated perfused guinea pig hearts.

Platelet-activating factor (PAF) has been termed an important mediator of cardiovascular shock due to immunological reactions, including anaphylaxis and endotoxic reactions. Previous studies have shown that PAF is a potent cardiodepressive agent inducing a drastic coronary constriction and a sustained impairment of myocardial contractility. In this study, an attempt was made to further characterize the prolonged PAF effects on coronary circulation and myocardial contractile force in the isolated guinea pig heart perfused at constant pressure. An intracoronary PAF bolus (0.18 nmol, related to coronary flow rates of 1 ml/min) induced a precipitous decrease of coronary flow rates, left ventricular pressure, and left ventricular contraction (peak positive dP/dt), which was followed by a slow increase reaching new steady state after 15 min (-48%, -40%, -42% below baseline, respectively). If the specific PAF antagonist WEB 2086 (3.65 nmol/min, related to coronary flow rates of 1 ml/min) was infused 30 min after PAF administration, the prolonged PAF-mediated cardio-depressive effects were rapidly reversed. Several studies indicate that PAF induces a down regulation of beta-adrenoreceptors in different cell types, including human lung tissue. Therefore, a further objective of the study was to evaluate whether PAF selectively impairs the positive inotropic effects of beta-receptor agonists or also inhibits the contractile effects of inotropic drugs, which are known to enhance cardiac contractility independently of beta-receptors. In these experiments, the beta-agonist isoproterenol and the H2-agonist impromidine were administered as intracoronary boluses (0.35 nmol and 0.14 nmol, respectively, related to coronary flow rates of 1 ml/min) prior to PAF injection and 30 min after PAF.(ABSTRACT TRUNCATED AT 250 WORDS)