Inter-individual Comparison of Gadobutrol and Gadoteridol Tissue Time-intensity Profiles for Dynamic Susceptibility Contrast Perfusion MR Imaging.

PURPOSE: Gadobutrol is a gadolinium-based contrast material (GBCM) with a high concentration of gadolinium and high relaxivity. Our purpose was to evaluate the signal intensity profiles in brain tissue for the bolus width and degree of signal change after bolus injection using an echo planar dynamic susceptibility contrast (DSC) sequence. We compared gadobutrol to gadoteridol using various injection speeds and saline flush volumes. METHODS: We studied 97 patients who underwent brain MRI. Datasets for perfusion studies were acquired using a 3T scanner with an echo planar imaging (EPI) sequence. The injection protocols were set up with combinations of injection speed and saline flush volume for both gadobutrol and gadoteridol. The full width at half maximum (FWHM) and the maximum signal change ratio (SCRmax) of the time intensity curves were measured. RESULTS: The FWHM did not show a statistically significant difference according to injection speed, flush volume, or type of GBCM. The SCRmax showed a greater change with a faster injection speed, larger saline flush, and gadobutrol administration. The difference between gadobutrol and gadoteridol became smaller with a faster injection speed and a larger saline flush. CONCLUSION: The maximum signal drop was larger with gadobutrol when the injection speed was slow and the saline flush was small. Thus, gadobutrol may be useful to obtain a better profile for DSC perfusion MRI in conditions requiring a slower injection speed and/or a smaller volume of saline flush.

Clinical usefulness of MLCs in robotic radiosurgery systems for prostate SBRT.

Stereotactic body radiation therapy (SBRT) using recently introduced multileaf collimators (MLC) is preferred over circular collimators in the treatment of localized prostate cancer. The objective of this study was to assess the clinical usefulness of MLCs in prostate SBRT by comparing the effectiveness of treatment plans using fixed collimators, variable collimators, and MLCs and by ensuring delivery quality assurance (DQA) for each. For each patient who underwent conventional radiation therapy for localized prostate cancer, mock SBRT plans were created using a fixed collimator, a variable collimator, and an MLC. The total MUs, treatment times, and dose-volume histograms of the planning target volumes and organs at risk for each treatment plan were compared. For DQA, a phantom with a radiochromic film or an ionization chamber was irradiated in each plan. We performed gamma-index analysis to evaluate the consistency between the measured and calculated doses. The MLC-based plans had an ~27% lower average total MU than the plans involving other collimators. Moreover, the average estimated treatment time for the MLC plan was 31% and 20% shorter than that for the fixed and variable collimator plans respectively. The gamma-index passing rate in the DQA using film measurements was slightly lower for the MLC than for the other collimators. The DQA results acquired using the ionization chamber showed that the discrepancies between the measured and calculated doses were within 3% in all cases. The results reinforce the usefulness of MLCs in robotic radiosurgery for prostrate SBRT treatment planning; most notably, the total MU and treatment time were both reduced compared to the cases using other types of collimators. Moreover, although the DQA results based on film dosimetry yielded a slightly lower gamma-index passing rate for the MLC than for the other collimators, the MLC accuracy was determined to be sufficient for clinical use.

Reactivation of hepatitis and lamivudine therapy in 11 HBsAg-positive renal allograft recipients: a single centre experience.

BACKGROUND: In hepatitis B virus (HBV) surface antigen (HBsAg) (+) renal allograft recipients, the mortality associated with liver disease reaches 37-78%. An antiviral agent, lamivudine, has recently been reported to be safe and effective for preventing hepatic damage in these patients, although either resurgence of HBV-DNA levels after discontinuation or emerging resistant HBV mutants caused by long-term administration are still unsettled. METHODS: Between July 1976 and December 2003, 555 renal transplantations were performed in our centre. Of these, 11 patients who were HBsAg (+) at the time of transplantation (2.0%) were selected for this study. We investigated the incidence of hepatitis reactivation for three yr after transplantation and their clinical courses, including the efficacy of lamivudine therapy in seven of the 11 patients. RESULTS: Six episodes of hepatitis reactivation developed in five of the 11 patients (45.5%) within three yr after transplantation. Five episodes of six occurred within four months after transplantation. The patient who underwent the most severe reactivation needed intensive care including lamivudine administration and plasma exchange. Lamivudine caused no severe adverse effects and HBV-DNA levels dropped to under measurable levels within four months after lamivudine administration in all patients. Resistant HBV mutant emerged in only one patient, who had the longest lamivudine administration of 49 months. CONCLUSIONS: For HBsAg (+) renal allograft recipients, careful monitoring of HBV-DNA levels and timely administration of lamivudine could prevent hepatic damage caused by reactivation of hepatitis.

Severe elevations of FK506 blood concentration due to diarrhea in renal transplant recipients.

BACKGROUND: The rate of metabolism in the intestine of oral administered FK506 decreases as FK506 passes on to the lower intestine. In transplant recipients with diarrhea given oral FK506, the main areas for absorption of FK506 shift to the lower intestine, where the ability to metabolize FK506 is weaker. Therefore it is considered likely that when FK506 is administered to recipients with diarrhea, the blood concentration of FK506 will be higher. MATERIAL AND METHODS: Twenty recipients experiencing episodes of diarrhea were investigated to determine the trough level of FK506 and the time required for the FK506 trough level to return to the level that obtained before diarrhea. AUC0-4h and Cmax of FK506 were investigated in eight recipients. In cases with severe diarrhea, the daily fluctuations of FK506 blood concentration were also investigated. RESULT: The FK506 trough level (p < 0.0001), AUC (p = 0.0173), and Cmax (p = 0.0173) were found to be significantly higher during episodes of diarrhea. In almost all cases, it took between 2 and 4 wk for the elevated FK506 trough level to return to its previous level following a bout of diarrhea. In the daily fluctuations of FK506 concentration, Tmax was prolonged. In some cases, the concentration was highest just before administration of FK506, when it should have been at trough level. CONCLUSIONS: Diarrhea caused significant elevations of trough level, AUC0-4h and Cmax of FK506, and the prolongation of Tmax in renal transplant recipients administered FK506.

Skew in T-cell receptor usage and clonal T-cell expansion in patients with chronic rejection of transplanted kidneys.

BACKGROUND: It is not known whether alloreactive T cells are involved in chronic rejection of transplanted kidneys. The aim of the present study was to determine the involvement of T cells in the chronic graft rejection. METHODS: T-cell receptor (TCR) variable region alpha-chain and TCR variable region beta-chain repertoires were analyzed in peripheral blood mononuclear cells. T-cell clonalities were analyzed by complementarity-determining region 3 size spectratyping. RESULTS: A significant increase in the frequencies of one or more TCR variable region alpha-chain and TCR variable region beta-chain segments was detected in 13 and 15 of the 24 kidney transplant recipients, respectively. The extent of the skew in the TCR usage was correlated with the levels of clonal T-cell expansion, indicating that the clonally expanding T cells were responsible for the skew in the TCR usage. The levels of the skew in the TCR usage and clonal T-cell expansion were significantly greater in the recipients with a graft failure than in those with a stable graft function ( P=0.0081 and P=0.012, respectively). These results indicate that the clonally expanding T cells in the periphery may be related to graft rejection. The percent increase in the serum creatinine levels, which reflected the deterioration of the kidney functions, was significantly higher in the recipients who showed high levels of clonal T-cell expansion than in those who did not ( P=0.021). CONCLUSIONS: The results demonstrate that clonal T-cell expansion in the periphery has a negative impact on the long-term graft functions, and that analysis of the clonal T-cell expansion in peripheral blood mononuclear cells provide significant information on the fate of the transplanted kidney.

Prophylactic deoxyspergualin treatment in living-related renal-transplant recipients transfused with donor-specific blood.

BACKGROUND: Deoxyspergualin (DSG) prophylaxis has improved long-term graft survival in living-related renal-transplant recipients transfused with donor-specific blood (DST). We examined the influence of acute rejection (AR) on graft survival in these patients. METHODS: The study groups consisted of either historic control recipients without DSG (group A, n=64, 1985-1989) and recipients with DSG as the initial immunosuppressive agent (group B, n=76, 1989-1995). Both groups received DST from a one-haplotype identical donor and were treated with cyclosporine-based immunosuppression. Rejection was classified into accelerated rejection (Acc, within 5 days), AR (from 6 days-3 months), and late AR (LAR, from 4 months-1 year). RESULTS: Overall 5-year graft survival rates were significantly higher in group B than group A (89.5 vs. 73.4%, P=0.0070). Each group was then subdivided on the basis of whether or not they had an episode of Acc, AR, or LAR. In group A, 5-year graft survival rate was not affected the presence or absence of Acc (75.0 vs. 73.1%), and it was influenced significantly by the presence or absence of AR (50.0 vs. 85.7%, P=0.0012) or LAR (46.7 vs. 81.6%, P<0.0001). In group B, 5-year graft survival did not change significantly by the presence or absence of Acc (100 vs. 88.7%), AR (81.8 vs. 92.6%), or LAR (81.0 vs. 92.7%). CONCLUSIONS: Prophylactic use of DSG in living-related renal-transplant recipients treated with DST improves long-term graft survival, even in patients with AR episodes.