NMR-based metabolomics in real-time monitoring of treatment induced toxicity and cachexia in head and neck cancer: a method for early detection of high risk patients.

INTRODUCTION: Nutritional treatment in head and neck squamous cell carcinoma cancer (HNSCC) patients undergoing radio-/chemo-radiotherapy (RT/CHRT) is complex and requires a multidisciplinary approach. In this study the real-time dynamic changes in serum metabolome during RT/CHRT in HNSCC patients were monitored using NMR-based metabolomics. OBJECTIVES: The main goal was to find the metabolic markers that could help prevent of acute radiation sequelae (ARS) escalation. METHODS: 170 HNSCC patients were treated radically with RT/CHRT. Blood samples were collected weekly, starting from the day before the treatment and stopping within the week after the RT/CHRT completion, resulting in a total number of 1328 samples. 1H NMR spectra were acquired on Bruker 400 MHz spectrometer at 310 K and analyzed using principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Additional statistical analyses were performed on the quantified metabolites. RESULTS: PCA has detected a group of distinct outliers corresponding to ketone bodies (3HB, Ace, AceAce). These outliers were found to identify the individuals at high risk of weight loss, mainly by the 3HB changes, which was confirmed by the patients' medical data. In the OPLS-DA models a transition from the lowest to the highest weight loss is seen, defining the metabolic time trajectories for the patients from the studied groups during RT/CHRT. 3HB is a relatively sensitive marker that allows earlier identification of the patients at higher risk of > 10% weight loss. CONCLUSION: Our findings indicate that metabolic alterations, characteristic for malnutrition or cachexia, can be detected already at the beginning of the treatment, making it possible to monitor the patients with a higher risk of weight loss.

Effect of Successful Treatment of Hepatitis C Virus Infection Recurrence With Direct-Acting Antiviral Agents on Physical Performance in Liver Transplant Recipients.

BACKGROUND: Hepatitis C virus (HCV) infection deregulates function of many organs and systems, affecting patient's daily functioning. The results of treatment of HCV infection recurrence after liver transplantation have improved significantly as a result of the introduction of direct-acting antiviral agents (DAA). This study was aimed at prospective assessment of the effect of HCV elimination with DAA on physical performance of liver transplant recipients. METHODS: Eight women and 21 men, median age 61.3 (range, 20.1-71.5) years, participated in the study. Assessment of serum total bilirubin, alanine and aspartate aminotransferase, muscle strength, body composition, and 6-minute walk test (6MWT) were performed before treatment and 12 weeks after the end of the treatment period. RESULTS: In the 6MWT test we observed significant subjective (dyspnea: 58.3% pretreatment vs 27.6% posttreatment, P = .018; fatigue: 96.6% pretreatment vs 51.7% posttreatment, P = .0001) and objective improvement (distance: 415.4 meters pretreatment vs 505.2 meters posttreatment, P < .0000001). We did not observe an increase in muscle mass nor improvement in blood biochemical parameters. CONCLUSION: A significant objective and subjective improvement in physical performance was seen in liver transplant recipients after successful treatment of HCV infection with DAA.

Outcomes of Prolonged Treatment With Intravenous Immunoglobulin Infusions for Acute Antibody-mediated Rejection in Kidney Transplant Recipients.

BACKGROUND: Treatment of antibody-mediated rejection (AMR) is one of the main problems after kidney transplantation (KTx). The results of intensive AMR treatment with plasmapheresis (PF) and repeated infusions of intravenous immunoglobulin (IVIg) are presented. METHODS: Diagnosis of AMR was based on graft biopsy and the presence of donor-specific antibodies (DSAs). AMR therapy consisted of 5 PF and IVIg infusions given after the last PF. Subsequent IVIg doses were given every 4 weeks for 6 months. Graft biopsy and DSA assessment were repeated at the end of the treatment (ET). RESULTS: Four women and 10 men were included in our study; mean time from KTx to AMR was 79 (range, 3-193) months. During the treatment, 4 patients had graft failure. Graft function at baseline was significantly worse (P = .02) in this group compared with patients who completed the therapy. At baseline, mean flourescence intensity (MFI) was 6574 (range, 852-15,917) in the whole group, 7088 (range, 1054-15,917) in patients who completed treatment, and 4828 (range, 852-11,797) in patients who restarted hemodialysis. At ET, DSA MFI decreased in 8 of 10 patients (80%) who completed the therapy. The MFI decrease was 3946 (range, 959-11,203). Control graft biopsies revealed decreased intensity of C4d deposits in peritubular capillaries in 7 patients (78%) and decreased peritubular capillaritis in 2 patients (22%). CONCLUSION: Intensive, prolonged AMR therapy with PF and IVIg resulted in a decrease in DSA titer and intensity of C4d deposits, but was not associated with reduction of microcirculation inflammation. Treatment was ineffective in patients with baseline advanced graft insufficiency.

Kidney Transplant Recipients With Rheumatic Diseases: Epidemiological Data From the Polish Transplant Registries 1998-2015.

Chronic kidney disease (CKD) is a common complication of rheumatic disorders. We analyzed the incidence of different rheumatic conditions as a primary diagnosis of end-stage renal disease (ESRD) in kidney transplant recipients in Poland. Data were received from the national waiting list for organ transplantation (Poltransplant) registries. Primary diagnosis leading to ESRD were analyzed in 15,984 patients who received kidney transplants between 1998 and 2015. There was no information about primary diagnosis in 4981 cases (31%) and in 1482 cases (9%) the diagnosis was described as unknown. Rheumatic diseases were specified in 566 (5.14%) kidney transplant recipients: lupus erythematosus, (systemic lupus erythematous nephritis) in 211 (1.92%), vasculitis in 176 (1.60%), amyloidosis AA in 82 (0.75%), hemolytic uremic syndrome in 59 (0.54%), secondary glomerulonephritis in 24 (0.22%), scleroderma in 9 (0.08%), rheumatoid arthritis in 4 (0.04%) and Sjögren syndrome in 1 (0.01%). Graft survival at 1 and 5 years were significantly better in the nonrheumatic versus rheumatic group (90 vs 87% and 76 vs 72% respectively, P = .04). Recipient survival at 5 years was significantly better in the nonrheumatic versus the rheumatic group (88 vs 84%, P = .02). Our study showed that systemic lupus erythematosus and systemic vasculitides are the major rheumatic causes of ESRD in the Polish population. Long-term graft and recipient survival were significantly better in the nonrheumatic versus the rheumatic group in the Poltransplant cohort.

Clinical Significance of Gastrointestinal Carriage of Klebsiella Pneumoniae-Producing Extended-Spectrum Beta-Lactamases in Kidney Graft Recipients.

The burden of Klebsiella pneumoniae (KP) producing extended-spectrum beta-lactamases (ESBL+) urinary tract infections (UTIs) is a growing problem after kidney transplantation (KTX). The study was aimed at evaluating the incidence of KP ESBL+ gut colonization in KTX recipients and its correlation with clinical outcomes with special regard to UTIs. The study included all KTX patients hospitalized in our department between January 2014 and December 2016. During this period 2018 KTX patients were admitted: 605 in 2014, 750 in 2015, and 663 in 2016, respectively. Screening for drug-multiresistant Enterobacteriaceae gut carriage was performed in 104 patients (2014), 122 (2015), and 166 (2016). In 2014, 2015, and 2016, 18 (17.3%), 26 (21.3%), and 30 (18.1%) patients had positive test results, and 44 (42.3%), 36 (29.5%), and 45 (27.4%) KTX patients were diagnosed with KP ESBL+ UTI. In 2014, KP ESBL+ UTI was diagnosed in 30 (34.9%) cases with negative anal swab and in 14 patients (77.8%) with positive test result (P = .0008). In 2015, KP ESBL+ UTI was diagnosed in 21 patients (21.9%) with negative anal swab and in 15 (57.7%) with positive test result (P = .0004). In 2016, KP ESBL+ UTI was diagnosed in 24 patients (17.8%) with negative anal swab and in 21 (72.4%) with positive test result (P = .000001). In conclusion, we have revealed a strong association between gut K. pneumoniae colonization, female sex, and MPA intake and KP ESBL+ urinary tract infections in kidney transplant recipients. Our results indicate the very important role of KP ESBL+ screening, while strategies of identified carriers require further research.

Drug Susceptibility Assessment in Stenotrophomonas Maltophilia Strains Isolated From the Blood of Organ Transplantation Recipients in a Warsaw Teaching Hospital During 2011 to 2014.

BACKGROUND: Blood infections with multidrug-resistant Gram-negative carbapenem-resistant bacilli are particularly dangerous and challenging to treat in organ transplant recipients. Resistance to carbapenems may be acquired, for example, in Enterobacteriaceae, Pseudomonas, or Acinetobacter spp. or innate, for example, in Stenotrophomonas maltophilia. The purpose of this study was to analyze blood infections caused by S maltophilia in organ transplant recipients and to compare drug susceptibility of these bacteria and the same species isolated from the blood of other inpatients. METHODS: A total of 26 S maltophilia strains isolated from blood samples of 26 patients (including 14 liver or kidney transplant recipients) hospitalized during 2011 to 2014 were evaluated in this study. Antibiotic susceptibility was determined via E-test and disk diffusion methods. RESULTS: Stenotrophomonas maltophilia strains isolated from blood exhibited sensitivity to trimethoprim/sulfamethoxazole (100%), levofloxacin (96.2%), ciprofloxacin (92.3%), ticarcillin/clavulanic acid (80.8%), and ceftazidime (53.9%). CONCLUSIONS: Because appropriate antibiotic therapy in the case of S maltophilia differs from the standard empirical therapy administered in the case of most other Gram-negative bacilli, early identification of this pathogen is of particular significance. The use of antibiotics to which this pathogen is sensitive eliminates the infection and helps avoid graft loss.

Successful Treatment of Urinary Tract Infection in Kidney Transplant Recipients Caused by Multiresistant Klebsiella pneumoniae Producing New Delhi Metallo-Beta-Lactamase (NDM-1) With Strains Genotyping.

BACKGROUND: Klebsiella pneumoniae New Delhi metallo-beta-lactamase-1 (NDM-1) strains have recently become a new threat in kidney transplant recipients due to the strains' resistance to almost all antibiotics, including carbapenems. METHODS: We present a case series of 3 patients with urinary tract infections (UTIs) caused by multiresistant K pneumoniae NDM-1 strains who were treated with the same protocol. Genotyping sequencing with pulsed-field gel electrophoresis was performed in all cases. RESULTS: All patients were male and had undergone kidney transplantation 4, 7, and 8 months, respectively, before the admission. Combined antibiotic therapy consisting of imipenem/cilastatin in maximal doses, gentamicin and/or colistin for 21 to 27 days, followed by oral fosfomycin, was used in all cases. There were no further UTI episodes in 2 patients at the 12-month visit. Three months after initial treatment, the third patient presented with leukocyturia with no clinical symptoms and a urine culture positive for K pneumonia NDM-1 strain. Interestingly, the strain was susceptible to trimethoprim/sulfamethoxazole despite resistance in previous urine culture samples. The patient was successfully treated with trimethoprim/sulfamethoxazole 2 × 960 mg/d for 3 weeks followed by 480 mg/d and 3 doses of fosfomycin. Genotyping sequencing revealed identical DNA restriction fragments in bacterial strains from 2 patients. In the third case, although a difference in 2 restriction fragments was observed, the strain was considered related to the others. CONCLUSIONS: In cases of UTI caused by K pneumoniae NDM-1 strains, prolong combined treatment followed by oral fosfomycin prophylaxis can be successful. Strain genotyping should be performed to optimize further treatment protocols in such cases.

Contraception in women after organ transplantation.

INTRODUCTION: Organ transplantation has improved the quality and length of life for many people suffering from end-stage diseases, among them women of reproductive age. Therefore, it has made pregnancy possible for those previously unable to conceive. Nevertheless, conception itself should be desired and properly timed in these specific patients to ensure the best possible perinatal outcome. OBJECTIVE: The objective of the study was to assess whether female graft recipients apply proper family planning methods and use effective contraception. METHODS: In a single-center, observational study, information was collected using a self-administered questionnaire distributed among 100 female graft recipients (post-transplant group [TG]) and 67 healthy female volunteers (control group [CG]). The survey covered data regarding present menstrual patterns, sexual activity, gynecological counseling, and contraceptive methods used. RESULTS: Female graft recipients were more sexually active after than before transplantation (87% vs 64%, P = .0001) and equally active as controls. Sexually active post-transplantation patients used contraception less frequently than sexually active controls (51.72% vs 82.76%, P < .0001). Condoms were the most frequently used method in TG, and oral contraception in CG. Oral contraception was used more rarely by counseled graft recipients than by counseled controls (3.9% vs 60.7%, P < .0001). After counseling, intrauterine device usage increased and oral contraception usage decreased in TG. Among women with chronic diseases, intrauterine device was used more often in TG (4% vs 0%), whereas oral contraception was used more often in CG (8.3% vs 50%, P < .0001). CONCLUSIONS: Despite the fact that post-transplantation women of reproductive age have many indications for highly effective contraception, only few of them actually use it. Contraceptive counseling has to be included as part of routine post-transplantation care by all health professionals involved in the management of female graft recipients of reproductive age.

Molecular analysis of carbapenem-resistant strains of Pseudomonas aeruginosa isolated from patients hospitalized in various transplantation wards between 2008 and 2011.

BACKGROUND: Recent years have seen a concerning increase in the number of carbapenem-resistant Pseudomonas aeruginosa strains. P aeruginosa is one of the most dangerous factors causing nosocomial infections, and immunosuppressed patients constitute a special risk group. The purpose of our study was to conduct a molecular analysis of 22 clinical isolates of carbapenem-resistant P aeruginosa obtained between 2008 and 2011. MATERIALS AND METHODS: Metallo-beta-lactamase (MBL) phenotype tests were conducted. A polymerase chain reaction technique was used to detect VIM, IMP, NDM, and GIM carbapenemase-encoding genes. The minimum inhibitory concentrations were determined for imipenem, meropenem, and doripenem. Molecular typing was conducted with the use of restriction fragment length polymorphism/pulsed-field gel electrophoresis (RFLP-PFGE). RESULTS: Of the 22 strains initially resistant to at least one carbapenem, we selected 18 that exhibited the MBL phenotype. Of those 18, we identified 15 strains expressing VIM carbapenemase-encoding genes. None of the other evaluated genes were detected. VIM-positive isolates exhibited higher levels of resistance than the other ones. The RFLP technique revealed 10 different PFGE types and 6 epidemic foci. Identical strains were isolated over the period of up to 3 years. CONCLUSIONS: The reason for resistance to carbapenems in the majority (68%) of P aeruginosa strains isolated at the evaluated hospital was the presence of VIM carbapenemase. It is safe to say that the VIM carbapenemase is responsible for a higher level of resistance than unidentified mechanisms. Carbapenem-resistant strains of P aeruginosa spread clonally within individual wards and are likely to be of hospital origin.

Low noise measurement system for determination of the critical currents in superconducting tapes by a pulse method.

Steady state measurements of the high critical currents in superconducting composite wires and tapes might be burdened with some errors. The origin of the errors is mainly associated with the Joule heat generated at current leads contacts, which at high transport currents can considerably increase temperature of an investigated sample wire. To avoid this unwanted heating phenomenon pulsed current methods are widely used. A waveform of the current pulse is usually shaped by means of a series RLC circuit with the subcritical dumping condition. Measurement results (i.e., a value of current peak, its time derivative, and a voltage drop along a superconducting sample) are recorded by means of a 4-channels, 12-bit resolution, 50 ns sampling time, digital recorder. Very low noise, broadband, voltage preamplifiers, based on rf bipolar transistors, were designed and fabricated. From the data, current-voltage characteristics are plotted and then the critical currents of investigated tapes are determined. Presented in the work our home-made, low noise, measurement setup allows to obtain a current pulse of about 4000 A at duration time of several milliseconds.

Rehabilitation and 6-minute walk test after liver transplantation.

BACKGROUND: Measurement of exercise capacity is an integral element to assess patients after surgery. Although the 6-minute walk test (6MWT) provides information regarding functional capacity, response to therapy, and prognosis across a range of conditions, its applicability for liver transplant recipients remains to be established. The aim of our study was to examine whether the 6MWT in combination with a subjective rating of perceived exertion (Borg Scale [BS]) could be used to evaluate exercise capacity among patients after liver transplantation (OLT). METHODS: Thirteen consecutive subjects were enrolled in this single-center study during routine rehabilitation of the 6MWT and BS. At days 7 and 14 after OLT seeking to assess objective and subjective exercise capacities, we recorded basic clinical parameters, including body weight, blood pressure, heart rate and temperature. The results as compared between days 7 and 14 were related to the reference values for age-, height- and weight-matched healthy subjects. RESULTS: On day 7, normal 6MWT was achieved by one patient and at day 14-, by three patients. At days 7 and 14, the average distances of 6MWT were 326.7 m and 421 m, respectively (P<.05), indicating a significant increase in exercise capacity. The average BS rating did not change significantly between days 7 and 14, indicating, that the increased exercise capacity was achieved without excessive effort. CONCLUSIONS: Our study indicated that the 6MWT and BS may represent inexpensive and safe assessment methods for exercise capacity after OLT. This evaluation may be helpful to plan and optimize post-OLT rehabilitation.

Strains of Klebsiella pneumoniae producing extended spectrum beta-lactamases, isolated from organ recipients.

OBJECTIVE: The aims of this work were to define the effectiveness of identification of the extended-spectrum beta-lactamases (ESBL) phenotype, and to define the genotype of Klebsiella pneumoniae ß-lactamase. MATERIALS AND METHODS: We identified ESBL phenotypes in 110 strains of K pneumoniae isolated from samples from patients of transplantation wards, using the double-disk synergy test (DDST). For the chosen strains, polymerase chain reaction (PCR) was applied to detect genes determining SHV, CTX-M, and TEM. RESULTS: We showed synergism of clavulanic acid and investigated antibiotics including ceftazidime (89.1%), cefotaxime (80%), and aztreonam (82.7%) against ESBL-positive strains PCR revealed that TEM and CTX-M were present in 88.89% of strains. CONCLUSIONS: The ESBL mechanism of resistance is frequent among K pneumoniae strains isolated from transplant recipients. Strains with simultaneous synthesis of more than one beta-lactamase predominated.

The dominant sequence types of vancomycin-resistant Enterococcus faecium among transplantation ward patients.

OBJECTIVES: Vancomycin-resistant enterococci (VRE) frequently cause therapeutic problems and provide information about the epidemiological condition of the ward. MATERIALS AND METHODS: VRE isolated from patients on transplantation wards in 2007-2008 were compared using 2 molecular methods: RFLP-PFGE (restriction fragment length polymorphism-pulse field gel electrophoresis) and MLST (multilocus sequence typing). RESULTS: The analysis covered 29 Enterococcus faecium strains resistant to glycopeptides, each from a different patient. All organisms were typed using 2 molecular methods. MLST results were compared with an international base. The 30 examined strains belonged to 8 different worldwide known sequence types. All could be recognized as representatives of a single clonal complex CC17. CONCLUSION: Both methods of typing appeared to be useful to asses the epidemiological condition of the investigated wards.

A threat of the Klebsiella pneumoniae carbapenemase-producing strains among transplant recipients.

BACKGROUND: Infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are associated with increased therapeutic failure and mortality. Our laboratory recognized several strains producing KPC, most of which originated from transplantation ward patients. MATERIALS AND METHODS: All strains of K pneumoniae resistant to at least 1 carbapenem isolated in 2010 were examined for KPC production by disc diffusion and then verified by molecular methods. RESULTS: All positive strains originated from 7 patients. Six of them were from transplantation wards. None of the KPC-producing strains was isolated from the patient's blood. CONCLUSIONS: A quick, accurate diagnosis of KPC-producing strains enabled immediate isolation of carriers or infected persons. Isolation prevented spread of dangerous strains among immunocompromised patients and reduced the possibility of serious infections.

Optimization of the first order gradiometer for small sample magnetization measurements using pulse integrating magnetometer.

In the paper we present an analytical calculation method for determination of the sensitivity of a pulse field magnetometer working with a first order gradiometer. Our considerations here are especially focused on a case of magnetic moment measurements of very small samples. Derived in the work analytical equations allow for a quick estimation of the magnetometer's sensitivity and give also the way to its calibration using the sample simulation coil method. On the base of the given in the paper calculations we designed and constructed a simple homemade magnetometer and performed its sensitivity calibration.

Present data on organ donation and transplantation in Poland.

At present, organ transplantation activity in Poland is located in the middle among European Union countries. There are appropriate law regulations, well-organized legal structures, well-educated transplant teams, good transplantation results, and case registries. There are 24 organ transplant teams in 20 centers, including 46 programs. Since 1966, over 18,000 organs have been transplanted 14,300 kidneys; 1800 livers; 1700 hearts; 250 kidney/pancreases and 30 lungs. Every year almost 1500 organs are procured from about 500 cadaveric heart-beating donors (9-14 per million people [pmp]) with 50 from living donors: 800 to 1000 kidneys (21-28 pmp); over 200 livers (5-6 pmp); and 60 to 100 hearts (1.6-2.7 pmp). National transplant registries are maintained in Poltransplant including a central registry of refusals (the policy of presumed consent with registered objection on donation after death is implemented), waiting lists, a cadaveric and living donor registry, and a transplant registry. There are still some actions that should be undertaken to strengthen the transplantation system in Poland, to increase organ availability, to enhance the efficiency and accessibility of transplantation systems, and to improve quality and safety: namely, increasing deceased donations to their full potential, appointing transplant coordinators in every hospital where there is the potential for organ donation, promoting quality improvement programs, and promoting living donation.

Safety and efficacy of steroid-free immunosuppression with tacrolimus and daclizumab in liver transplant recipients: 6-year follow-up in a single center.

BACKGROUND: Avoidance of steroid therapy after solid-organ transplantation has become a major challenge. Corticosteroid (CS)-free maintenance immunosuppression not only eliminates the well-known adverse effects but also may improve long-term outcome. OBJECTIVE: To investigate whether a CS-free regimen of tacrolimus (Tac) in combination with daclizumab (Dac) induction therapy provides adequate coverage after orthotopic liver transplantation. PATIENTS AND METHODS: This 6-year, single-center, retrospective study included 25 liver transplant recipients randomized to a Tac/CS regimen (n = 18) vs a Tac/Dac regimen (n = 7) according to the protocol of the MASTER (Monoclonal Antibodies vs STERoids) Study. RESULTS: No significant difference was observed in patient and graft survival between treatment arms: 94.4% in the Tac/CS group vs 71.4% in the Tac/Dac group. The incidence of biopsy-proved acute rejection episodes was 23.5% in the Tac/CS group vs 14.3% in the Tac/Dac group (P = NS). Total duration of hospitalization did not differ significantly between groups: 46.5 days in the Tac/CS group vs 73.9 days in the Tac/Dac group. Liver function as estimated using serum alanine aminotransferase and aspartate aminotransferase activity and bilirubin concentration, was not significantly different between the groups during 5 years posttransplantation. However, after 6 years, alanine aminotransferase activity was significantly greater in the Tac/Dac group compared with the Tac/CS group. CONCLUSIONS: A CS-free regimen of Tac/Dac is as effective as Tac/Cs in achieving good patient and graft survival. However, no substantial benefits insofar as the safety of Tac/Dac therapy were evident during long-term follow-up.

Transplant glomerulopathy: clinical and pathological correlations.

OBJECTIVE: Chronic transplant glomerulopathy (TG) is one of the leading causes of severe posttransplantation proteinuria and graft loss. Our current knowledge about risk factors for the development of TG, as well as factors that affect its dynamics and prognosis, is poor. We sought to describe the pathological and clinical risk factors and correlations of TG as well as parameters that influenced the survival of grafts with that pathology. MATERIALS AND METHODS: We retrospectively reevaluated 86 kidney transplant cases with TG that have been recognized on the basis of an indication biopsy since 1997. All TG as well as all pre-TG (previous) biopsies were characterized for the presence of C4d deposits in the graft. RESULTS: Younger recipient age and minimal immunosuppression due to drug withdrawal or suboptimal drug doses/blood levels within 3 to 6 months preceding the biopsy were associated with C4d deposition in peritubular capillaries (PTC; P = .0053 and P = .0365, respectively). Diffuse PTC-itis (P = .029, RR [95% confidence interval] = 3.349 [1.131-9.919]) and total interstitial inflammation score (P = .015, RR [95% confidence interval] = 9.662 [1.784-52.329]) were observed to show a negative impact on graft survival. C4d deposition in PTC and glomeruli, the level of pretransplantation sensitization, episodes of acute rejection, and C4d in previous (pre-TG) biopsies did not influence the survival of grafts with TG. CONCLUSIONS: Younger recipient age and minimal immunosuppression were associated with C4d positivity in grafts with TG. The survival of kidney grafts with TG was significantly affected by the magnitude of inflammation in the interstitium and PTC, but not by C4d positivity in PTC and glomeruli.

Sensitivity of the integrating pulse magnetometer with a first-order gradiometer.

Inductive magnetometers used for measurements in pulsed magnetic fields should have proper frequency characteristics. In the present work we describe the construction of an inductive magnetometer for measurements of the magnetic moment in pulsed magnetic fields, together with the calculation procedures for determination of its sensitivity. We present a method for determination of the effective coefficient of the coupling between the coils set (gradiometer) and cylindrical samples, as well as a method for calculation of the thermal noise in the measuring system. The determination of the effective coupling coefficient permits a straightforward connection of the value of the measured signal with the magnetic moment of the sample and calibration of the gradiometer in absolute units. In the work we also present, as examples, some experimental hysteresis loops of pulse magnetization measurements for some ferromagnetic samples and a single crystal of high temperature superconductor. The results were obtained using our homemade pulse magnet and magnetometer with a gradiometer designed and constructed on basis of presented here calculations.

Is Taurolidine a candidate for treatment of rheumatoid arthritis?

OBJECTIVE: To study the therapeutic potential of taurolidine (TRD), a derivative of taurine with known anti-inflammatory and anti-proliferative properties, in various experimental models of synovitis. METHODS: In vitro: fibroblast-like synoviocytes (RA FLS) isolated from the synovial tissue of patients with rheumatoid arthritis (RA) were cultured in the presence of either TRD or polyvinylpyrrolidine (PVP), the pharmaceutical stabilizer of TRD, which was used as a control. Proliferation of RA FLS and cytokine (IL-6 and IL-8) release were measured. In vivo: (A). The effect of systemic TRD treatment on the development of collagen-induced arthritis (CIA) in female DBA1/J mice was investigated. Mice were treated either with intraperitoneal injections of 1 ml of 2% Taurolin Boehringer Ingelheim (TRD +PVP) or with PVP as placebo. The incidence of arthritis, myeloperoxidase (MPO) activity in periarticular tissue, as well as serum concentration of IgG specific to collagen II (IgG alphaCII) were determined. (B). The effect of intra-articular TRD treatment was studied in rabbits with antigen-induced monoarthritis (AIA). After the induction of AIA of right knees rabbits were treated either with intra-articular injections of 0.5 ml of 2% Taurolin or 0.5ml PVP ( placebo). The animals were examined for clinical signs of arthritis and diameter of joints was measured. After termination of the experiment, the arthritic knees were examined and histopathology of the joints was assessed. In addition, serum amyloid A (SAA) concentration was measured. RESULTS: n vitro: TRD exerted cytotoxic effect on RA FLS when applied at concentrations >100 microM. TRD at non-cytotoxic concentrations, inhibited PDGF-triggered RA FLS proliferation, reduced IL-1beta - stimulated production of IL-6 and slightly decreased intracellular content of IL-8. In vivo: (A). Intraperitoneal treatment with Taurolin significantly reduced the incidence (30%) of CIA when compared to the control mice (79%). However, Taurolin failed to control the development of CIA in mice with high serum level of IgG alphaCII (>1000 U).(B). Intra-articular application of 2% Taurolin resulted in amelioration of AIA in all treated rabbits (reduced diameter of arthritic joints and smaller rise of SAA level as compared to the control animals). Histopathologic evaluation revealed pannus formation in both groups and extensive necrotic lesions of synovial tissue treated with TRD, suggesting synoviorthesis-like effect. CONCLUSION: Results from AIA and from in vitro RA FLS studies suggest that intra-articular administration of TRD could be used as a "pharmacological scalpel" to remove the inflamed synovium. Our data confirmed anti-inflammatory and anti-proliferative properties of TRD in all experimental models encouraging further studies which should evaluate its therapeutic potential in RA.