Cytomegalovirus infection following renal transplantation in patients administered low-dose rituximab induction therapy

Anti-CD20 antibody (rituximab) is recently being used as a B cell-depleting agent in renal transplantation (RTx). However, the incidence of infectious complications associated with rituximab therapy remains uncertain. We evaluated the incidence of cytomegalovirus (CMV) infection associated with rituximab therapy in RTx. A total of 83 patients were enrolled. The immunosuppressive regimen consisted of tacrolimus or cyclosporin, mycophenolate mofetil, methylprednisolone and basiliximab. In 54 patients, only one dose of rituximab (200 or 500 mg/kg body weight) was given before RTx. A total of 25 of 43 (58.1%) recipients who were CMV seropositive prior to RTx and who received rituximab induction therapy developed CMV infection, compared to 18 of 24 (75%) CMV seropositive recipients who did not receive rituximab therapy ( P  = 0.1676). A total of 8 of 11 patients who were CMV seronegative prior to RTx and who received rituximab developed CMV infection. However, CMV seroconversion was seen in all 8 of these infected patients. Low-dose rituximab induction therapy in renal transplant recipients appears to have no influence on the incidence of CMV infection and CMV seroconversion. However, we have to consider anti-CMV prophylaxis therapy, because of high incidents of CMV infection, especially for CMV seronegative recipients who received rituximab.     

Negative Impact of Blood Transfusion on Recurrence and Prognosis of Hepatocellular Carcinoma After Hepatic Resection

Background  In perioperative management of hepatic resection for hepatocellular carcinoma, excessive blood loss and blood transfusion greatly influence postoperative complications and prognosis of the patients. We evaluated the influence of blood products use on postoperative recurrence and prognosis of patients with hepatocellular carcinoma. Methods  The subjects were 66 patients who underwent elective hepatic resection for hepatocellular carcinoma without concomitant microwave or radiofrequency ablation therapy nor other malignancies between January 2001 and June 2006. We retrospectively investigated the influence of the use of blood products including red cell concentration and fresh frozen plasma on recurrence of hepatocellular carcinoma and overall survival. Results  In multivariate analysis, the dose of blood products transfusion was a significant predictor of disease-free and overall survival. Both disease-free and overall survival rates of those who were given blood products were significantly worse than those who did not receive. On the other hand, in univariate analysis of disease-free and overall survival after hepatic resection and clinical variables, the amount of blood loss was not a significant predictor of recurrence or death. Conclusion  Transfusion of blood products is associated with increased recurrence rate and worse survival after elective hepatic resection for patients with hepatocellular carcinoma.     

Three-dimensional brain phantom containing bone and grey matter structures with a realistic head contour

Introduction

A physical 3-dimensional phantom that simulates PET/SPECT images of static regional cerebral blood flow in grey matter with a realistic head contour has been developed. This study examined the feasibility of using this phantom for evaluating PET/SPECT images.

Methods

The phantom was constructed using a transparent, hydrophobic photo-curable polymer with a laser-modelling technique. The phantom was designed to contain the grey matter, the skull, and the trachea spaces filled with a radioactive solution, a bone-equivalent solution of K₂HPO₄, and air, respectively. The grey matter and bone compartments were designed to establish the connectivity. A series of experiments was performed to confirm the accuracy and reproducibility of the phantom using X-ray CT, SPECT, and PET.

Results

The total weight was 1997 ± 2 g excluding the inner liquid, and volumes were 563 ± 1 and 306 ± 2 mL, corresponding to the grey matter and bone compartments, respectively. The apparent attenuation coefficient averaged over the whole brain was 0.168 ± 0.006 cm^?1 for Tc-99 m, which was consistent with the previously reported value for humans (0.168 ± 0.010 cm^?1). Air bubbles were well removed from both grey-matter and bone compartments, as confirmed by X-ray CT. The phantom was well adapted to experiments using PET and SPECT devices.

Conclusion

The 3-dimensional brain phantom constructed in this study may be of use for evaluating the adequacy of SPECT/PET reconstruction software programs.     

Lethal and Mutagenic Effects of 252Cf Radiation in Cultured Human Cells

Summary

HeLa MR cells were exposed to radiation emitted from a man-made spontaneously fissioning isotope, californium-252. The neutron to gamma-ray ratio in the radiation dose was measured to be 2·0. The extrapolation number of the dose-survival curve was 1·3 and the Do was 200 cGy. A dose-dependent increase in mutation to 6-TG^r (6-thioguanine resistant) was observed. The relative biological effectiveness (r.b.e.) for cell killing of the neutrons from ²⁵²Cf, calculated relative to high-dose-rate X-rays, was 2·6 at 50 per cent survival. The r.b.e. for mutation induction was 2·7 at a mutation frequency of 5 × 10^?5 per surviving cell.     

Physical and clinical evaluation of new high-strip-density radiographic grids

The imaging performance of new high-strip-density (HSD) grids having 57 lines/cm was compared with that of conventional low-strip-density (LSD) grids having 33 or 40 lines/cm. The unique advantage of HSD grids is that, under most standard radiographic conditions, the grid lines are not noticeable on the final image, even if the grid is stationary. This is due to the combined effect of the high fundamental spatial frequency of HSD grids, the modulation transfer function of screen-film systems and of the human visual system, and scattered radiation. Monte Carlo simulation studies, phantom images, and clinical evaluation indicate that HSD grids can provide contrast improvement factors and Bucky factors that are comparable to or slightly better than those obtained with LSD grids. Therefore, it may now be possible to eliminate moving Bucky trays from radiographic tables and fluoroscopic devices.     

Imaging P-glycoprotein function in rats using [11C]-N-desmethyl-loperamide

Objective

One mechanism that may be responsible for drug resistance in epilepsy is the upregulation of P-glycoprotein (P-gp), a drug efflux pump, at the epileptogenic focus. In this study, we sought to evaluate the potential of a recently developed P-gp PET radiotracer, [¹¹C]N-desmethyl-loperamide ([¹¹C]dLop), for measuring P-gp function in the rat brain.

Methods

The precursor to [¹¹C]dLop was synthesized in two steps from commercially available starting materials and subsequently radiolabeled in one step using [¹¹C]methyl iodide. [¹¹C]dLop was then administered to two groups of rats, controls (n = 4) and those treated with a P-gp inhibitor (n = 8). Cyclosporin A (CsA, 50 mg/kg, n = 3) and tariquidar (TQ, 20 mg/kg, n = 5) were both used as P-gp inhibitors. MicroPET brain scans were performed for 120 min with arterial blood sampling. A one-tissue compartment model was used to estimate the distribution volume of radiotracer as the outcome measure of P-gp function.

Results

Plasma levels of parent [¹¹C]dLop decreased rapidly to <0.1 mean standardized uptake value (SUV) at 60 min. In controls, brain uptake of [¹¹C]dLop was very low (<0.1 mean SUV). In contrast, the mean SUVs were significantly higher in rats treated with CsA (0.51) or TQ (0.22). Estimation of distribution volumes was stable by 70 min. Estimated distribution volumes were significantly larger after P-gp inhibition (CsA = 7.3, TQ = 4.7) compared to controls (no inhibitor = 2.1).

Conclusions

The rat brain demonstrates significantly increased uptake of [¹¹C]dLop after P-gp inhibition. [¹¹C]dLop is a substrate of P-gp, and will serve as a promising radiotracer for studying P-gp function in the future.     

Three-dimensional SPECT reconstruction with transmission-dependent scatter correction

OBJECTIVE: The quality of single-photon emission computed tomography (SPECT) imaging is hampered by attenuation, collimator blurring, and scatter. Correction for all of these three factors is required for accurate reconstruction, but unfortunately, reconstruction-based compensation often leads to clinically unacceptable long reconstruction times. Especially, efficient scatter correction has proved to be difficult to achieve. The objective of this article was to extend the well-known transmission-dependent convolution subtraction (TDCS) scatter-correction approach into a rapid reconstruction-based scatter-compensation method and to include it into a fast 3D reconstruction algorithm with attenuation and collimator-blurring corrections. METHODS: Ordered subsets expectation maximization algorithm with attenuation, collimator blurring, and accelerated transmission-dependent scatter compensation were implemented. The new reconstruction method was compared with TDCS-based scatter correction and with one other transmission-dependent scatter-correction method using Monte Carlo simulated projection data of (99m)Tc-ECD and (123)I-FP-CIT brain studies. RESULTS: The new reconstruction-based scatter compensation outperformed the other two scatter-correction methods in terms of quantitative accuracy and contrast measured with normalized mean-squared error, gray-to-white matter and striatum-to-background ratios, and also in visual quality. Highest accuracy was achieved when all the corrections (i.e., attenuation, collimator blurring, and scatter) were applied. CONCLUSIONS: The developed 3D reconstruction algorithm with transmission-dependent scatter compensation is a promising alternative to accurate and efficient SPECT reconstruction.     

Comparison of Gd-DTPA-induced signal enhancements in rat brain C6 glioma among different pulse sequences in 3-Tesla magnetic resonance imaging

Background: T1-shortening contrast media are routinely used in magnetic resonance (MR) examinations for the diagnosis of brain tumors. Although some studies show a benefit of 3 Tesla (T) compared to 1.5T in delineation of brain tumors using contrast media, it is unclear which pulse sequences are optimal.

Purpose: To compare gadopentetate dimeglumine (Gd-DTPA)-induced signal enhancements in rat brain C6 glioma in the thalamus region among different pulse sequences in 3T MR imaging.

Material and Methods: Five rats with a surgically implanted C6 glioma in their thalamus were examined. T1-weighted brain images of the five rats were acquired before and after Gd-DTPA administration (0.1 mmol/kg) using three clinically available pulse sequences (spin echo [SE], fast SE [FSE], fast spoiled gradient echo [FSPGR]) at 3T. Signal enhancement in the glioma (E_T) was calculated as the signal intensity after Gd-DTPA administration scaled by that before administration. Pulse sequences were compared using the Tukey-Kramer test.

Results: E_T was 1.12±0.05 for FSE, 1.26±0.11 for FSPGR, and 1.20±0.11 for SE. FSPGR showed significantly higher signal enhancement than FSE and comparable enhancement to SE.

Conclusion: FSPGR is superior to FSE and comparable to SE in its ability to delineate rat brain C6 glioma in the thalamus region.     

Persistent subclinical rejection associated with nodular B-cell infiltrates in a renal transplant recipient

Abstract:  Recently, B-cell infiltrates in acute rejection grafts have attracted interest as an indicator of refractory rejection. Here, we report a case of deceased donor renal transplantation in a Japanese recipient operated overseas in which the recipient suffered from persistent tubulointerstitial rejection episodes associated with B-cell infiltrates. A 59-yr-old man with end-stage renal disease caused by immunoglobulin A nephropathy underwent deceased donor renal transplantation overseas in December 2005. The initial post-operative course was uneventful. The patient was referred to our hospital one month after transplantation. He maintained stable renal function throughout the follow-up period. The maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil and methylprednisolone. His serum creatinine concentration remained around 1.0 mg/dL, with no evidence of proteinuria. However, a discrepancy was detected between the renal function and the pathological findings. The pathology showed subclinical tubulointerstitial rejection with nodular B-cell infiltrates refractory to aggressive antirejection therapy. A steroid pulse and 15-deoxyspergualin were ineffective and the patient developed interstitial fibrosis and tubular atrophy by one yr after the transplantation, with persistent tubulitis and B-cell infiltrates. We treated the refractory rejection with B-cell infiltrates with a single 200 mg/body dose of rituximab and obtained an improvement. The pathological findings after administering rituximab consisted of mild tubulitis classified as Banff borderline, and elimination of the nodular B-cell infiltrates. At present, 20 months after renal transplantation, the patient continues to maintain stable renal function, with a good serum creatinine concentration (0.87 mg/dL).     

Tubulointerstitial nephritis and IgA nephropathy in a patient with advanced lung cancer treated with long-term gefitinib

A 52-year-old Japanese female was admitted to our hospital for microhematuria, proteinuria and progressive renal dysfunction. Two years prior to admission, she was diagnosed with lung adenocarcinoma and multiple bone and brain metastases, and was treated with gefitinib (250 mg/day). Treatment for 6 months induced partial response with 30% regression of the primary lung tumor, and resolution of metastatic tumors. After confirmation of the partial remission state, we performed percutaneous renal biopsy. Glomeruli showed mild to moderate mesangial proliferation, segmental endocapillary proliferation and occasional fibrocellular crescent formation. In addition, severe interstitial fibrosis and tubular atrophy relative to the degree of glomerular sclerosis were noted. Immunofluorescence microscopy showed predominant IgA deposition in the mesangial area. Electron microscopy revealed subepithelial and paramesangial electron-dense deposits. In consideration of the prognosis of lung cancer and complication of immunosuppressive treatment, we continued gefitinib only and closely followed-up the clinical course in the outpatient clinic. Sixteen months later, she continued to have proteinuria and microhematuria, and the severity of renal dysfunction was still the same. However, the lung cancer started to increase in size. This is quite an unusual case presenting histologically with tubulointerstitial nephritis and IgA nephropathy in a patient on long-term treatment with gefitinib.