Outcomes and native renal recovery following simultaneous liver-kidney transplantation.

With the increase in patients having impaired renal function at liver transplant due to MELD, accurate predictors of posttransplant native renal recovery are needed to select candidates for simultaneous liver-kidney transplantation (SLK). Current UNOS guidelines rely on specific clinical criteria for SLK allocation. To examine these guidelines and other variables predicting nonrecovery, we analyzed 155 SLK recipients, focusing on a subset (n = 78) that had post-SLK native GFR (nGFR) determined by radionuclide renal scans. The 77 patients not having renal scans received a higher number of extended criteria donor organs and had worse posttransplant survival. Of the 78 renal scan patients, 31 met and 47 did not meet pre-SLK UNOS criteria. The UNOS criteria were more predictive than our institutional criteria for all nGFR recovery thresholds (20-40 mL/min), although at the most conservative cut-off (nGFR ≤ 20) it had low sensitivity (55.3%), specificity (75%), PPV (67.6%) and NPV (63.8%) for predicting post-SLK nonrecovery. On multivariate analysis, the only predictor of native renal nonrecovery (nGFR ≤ 20) was abnormal pre-SLK renal imaging (OR 3.85, CI 1.22-12.5). Our data support the need to refine SLK selection utilizing more definitive biomarkers and predictors of native renal recovery than current clinical criteria.

Dorsal (AO/ASIF) pi-plate osteosynthesis in the treatment of distal intraarticular radius fractures.

The results and complications using the dorsal 2.4 mm 2.7 mm (AO/ASIF) pi-plate for the treatment of distal radius fractures were evaluated in a prospective study of 42 patients followed up clinically and radiologically and seven patients followed up with telephone call and radiological follow-up for an average time of 12.1 (range 4-32) months in a group of 50 patients with intraarticular distal radial fractures treated consecutively using this method. Twelve complications occurred in 10 patients including two extensor tendon ruptures, two transient cases of CRPS Type 1 (Reflex Sympathetic Dystrophy, Algodystrophy), two instances of screw loosening, three cases of posttraumatic carpal tunnel syndrome and three permanent sensory irritations on the dorsum of the hands. Using the AO score, there were 37 successful and 12 tolerable results, with no unsatisfactory outcomes. Using the NYOWR scale, there were 17 very good and 25 good results, with no satisfactory or poor outcomes. These results suggest that this osteosynthesis provides adequate fixation of comminuted distal intraarticular radius fractures with a reasonable incidence of complications.

Pharmacokinetics of 99mTc(Sn)- and 131I-labeled anti-carcinoembryonic antigen monoclonal antibody fragments in nude mice.

The biodistribution, radioimmunoimaging, and high pressure liquid chromatography activity profiles of 99mTc(Sn) and 131I-labeled anti-carcinoembryonic antigen monoclonal antibody fragments were compared. Nude mice, bearing specific (colon carcinoma, LS174T) and nonspecific (pancreatic carcinoma, MIA) xenografts were given injections of the respective radiolabeled antibody fragments and also of irrelevant 125I-labeled antibody fragments (MOPC-21). The animals were imaged at 24 h after being given injections, they were sacrificed, and biodistribution studies were performed. Results of the study showed high kidney uptake [48.6% injected dose (ID)/g +/- 8.1% (SD)] and low tumor uptake (1.5% ID/g +/- 0.6%) for 99mTc(Sn)-labeled fragments and higher uptake (4.4% ID/g +/- 0.6%) for 131I-labeled fragments, resulting in a higher localization index for the radioiodinated monoclonal antibody fragments. Imaging results showed good tumor visualization at 24 h after injection for the 131I-labeled fragments and poor tumor visualization with predominant kidney uptake for 99mTc(Sn)-labeled fragments. After radiolabeling, high pressure liquid chromatography analysis indicated that 131I was primarily associated with F(ab')2 fragments, whereas 99mTc was mostly associated with Fab' fragments.

Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin's lymphoma.

PURPOSE: Yttrium-90 ibritumomab tiuxetan (IDEC-Y2B8) is a murine immunoglobulin G1 kappa monoclonal antibody that covalently binds MX-DTPA (tiuxetan), which chelates the radioisotope yttrium-90. The antibody targets CD20, a B-lymphocyte antigen. A multicenter phase I/II trial was conducted to compare two doses of unlabeled rituximab given before radiolabeled antibody, to determine the maximum-tolerated single dose of IDEC-Y2B8 that could be administered without stem-cell support, and to evaluate safety and efficacy. PATIENTS AND METHODS: Eligible patients had relapsed or refractory (two prior regimens or anthracycline if low-grade disease) CD20(+) B-cell low-grade, intermediate-grade, or mantle-cell non-Hodgkin's lymphoma (NHL). There was no limit on bulky disease, and 59% had at least one mass > or = 5 cm. RESULTS: The maximum-tolerated dose was 0.4 mCi/kg IDEC-Y2B8 (0.3 mCi/kg for patients with baseline platelet counts 100 to 149,000/microL). The overall response rate for the intent-to-treat population (n = 51) was 67% (26% complete response [CR]; 41% partial response [PR]); for low-grade disease (n = 34), 82% (26% CR; 56% PR); for intermediate-grade disease (n = 14), 43%; and for mantle-cell disease (n = 3), 0%. Responses occurred in patients with bulky disease (> or = 7 cm; 41%) and splenomegaly (50%). Kaplan-Meier estimate of time to disease progression in responders and duration of response is 12.9+ months and 11.7+ months, respectively. Adverse events were primarily hematologic and correlated with baseline extent of marrow involvement with NHL and baseline platelet count. One patient (2%) developed an anti-antibody response (human antichimeric antibody/human antimouse antibody). CONCLUSION: These phase I/II data demonstrate that IDEC-Y2B8 radioimmunotherapy is a safe and effective alternative for outpatient therapy of patients with relapsed or refractory NHL. A phase III study is ongoing.

Radioimmunotherapy of relapsed non-Hodgkin's lymphoma with zevalin, a 90Y-labeled anti-CD20 monoclonal antibody.

Approximately 55,400 new cases of non-Hodgkin's lymphoma (NHL) are diagnosed each year, with the overall prevalence of the disease now estimated to be 243,000. Until recently, treatment alternatives for advanced disease included chemotherapy with or without external beam radiation. Based on the results of several clinical trials, the chimeric monoclonal antibody Rituximab has now been approved by the United States Food and Drug Administration as a treatment for patients with relapsed or refractory, low-grade or follicular, B-cell NHL. Several other monoclonal antibodies in conjugated and unconjugated forms have been evaluated in the treatment of NHL. Ibritumomab, the murine counterpart to Rituximab, radiolabeled with 90Y (Zevalin), is presently being evaluated in clinical trials. The success of radioimmunotherapy is dependent upon the appropriate choice of antibody, isotope, and chelator-linker. The Ibritumomab antibody targets the CD20 antigen. The antibody is covalently bound to the chelator-linker tiuxetan (MX-DTPA), which tightly chelates the isotope 90Y. To date, two Phase I/II Zevalin clinical trials have been completed in patients with low-grade, intermediate-grade, and mantle cell NHL. The overall response rate was 64% in the first trial and 67% in the later trial. Phase II and III trials are ongoing.

Estimation of hemopoietic potential by CFU-c and bone marrow scan in cancer patients.

The concentration of granulocyte-macrophage colonies in culture (CFU-c) in bone marrow cells was estimated, and bone marrow radionuclide scans were performed in a group of 15 cancer patients prior to bone marrow harvest for autologous transplantation. Preharvest CFU-c counts on iliac-crest bone marrow aspirates correlated very well with CFU-c counts from fresh and frozen-thawed bone marrows. Technetium-99m-sulfur colloid radionuclide scans showed that the distribution of total-body bone marrow and increased peripheral radionuclide uptake correlated with higher preharvest and harvest CFU-c counts. Bone marrow scan results were available in 1 h, whereas CFU-c counts took 14 days to obtain. Bone marrow scans may facilitate the clinical estimation of hemopoietic activity in patients under consideration for autologous bone marrow transplantation.

Biodistribution and dosimetry results from a phase III prospectively randomized controlled trial of Zevalin radioimmunotherapy for low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma.

UNLABELLED: Radiation dosimetry studies were performed in patients with non-Hodgkin's lymphoma (NHL) treated with 90Y Zevalin (90yttrium ibritumomab tiuxetan, IDEC-Y2B8) on a Phase III open-label prospectively randomized multicenter trial. The trial was designed to evaluate the efficacy and safety of 90Y Zevalin radioimmunotherapy compared to rituximab (Rituxan, MabThera) immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed NHL. An important secondary objective was to determine if radiation dosimetry prior to 90Y Zevalin administration is required for safe treatment in this patient population. METHODS: Patients randomized into the Zevalin arm were given a tracer dose of 5 mCi (185 MBq) (111)In Zevalin (111indium ibritumomab tiuxetan) on Day 0, evaluated with dosimetry, and then administered a therapeutic dose of 0.4 mCi/kg (15 MBq/kg) 90Y Zevalin on Day 7. Both Zevalin doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve Zevalin biodistribution. Following administration of (111)In Zevalin, serial anterior and posterior whole-body scans were acquired and blood samples were obtained. Residence times for 90Y were estimated for major organs, and the MIRDOSE3 computer software program was used to calculate organ-specific and total body radiation absorbed dose. Patients randomized into the rituximab arm received a standard course of rituximab immunotherapy (375 mg/m(2) weekly x 4). RESULTS: In a prospectively defined 90 patient interim analysis, the overall response rate was 80% for Zevalin vs. 44% for rituximab. For all patients with Zevalin dosimetry data (N=72), radiation absorbed doses were estimated to be below the protocol-defined upper limits of 300 cGy to red marrow and 2000 cGy to normal organs. The median estimated radiation absorbed doses were 71 cGy to red marrow (range: 18-221 cGy), 216 cGy to lungs (94-457 cGy), 532 cGy to liver (range: 234-1856 cGy), 848 cGy to spleen (range: 76-1902 cGy), 15 cGy to kidneys (0.27-76 cGy) and 1484 cGy to tumor (range: 61-24274 cGy). Toxicity was primarily hematologic, transient, and reversible. The severity of hematologic nadir did not correlate with estimates of effective half-life (half-life) or residence time of 90Y in blood, or radiation absorbed dose to the red marrow or total body. CONCLUSION: 90Y Zevalin administered to NHL patients at non-myeloablative maximum tolerated doses delivers acceptable radiation absorbed doses to uninvolved organs. Lack of correlation between dosimetric or pharmacokinetic parameters and the severity of hematologic nadir suggest that hematologic toxicity is more dependent on bone marrow reserve in this heavily pre-treated population. Based on these findings, it is safe to administer 90Y Zevalin in this defined patient population without pre-treatment (111)In-based radiation dosimetry.

Radioisotope scanning in inflammatory muscle disease.

Fourteen whole-body rectilinear bone scans using technetium 99m-polyphosphate were done in nine patients with well-documented inflammatory myopathy (either polymyositis or dermatomyositis). In all nine patients, the scans showed evidence of increased muscle labeling. Muscle uptake was markedly increased in one patient, moderately increased in two patients, and minimally increased in six patients. The degree of muscle labeling correlated with the severity of the muscle weakness at the time the scan was done. In four patients, who received high-dose corticosteroid treatment, muscle uptake was decreased following therapy. These findings suggest that radioisotope scanning may be useful in the diagnosis and management of patients with inflammatory muscle diseases.

A new radioisotope technique of splenic localization for radiation treatment.

A new technique of splenic localization, before initiating radiation therapy in patients with Hodgkin's disease, is described. We find this method of splenic localization economical and accurate.

The paper spot test: a rapid method for quantitating stannous concentrations in radiopharmaceutical kits.

We have developed a simplified, semiquantitative test for the determination of stannous tin in pyrophosphate and other tin-containing radiopharmaceuticals, excluding those stabilized with ascorbic acid and MAA preparations. The test involves the formation and disappearance of a positive red color complex in the presence of Sn(II) and in acidified porphyrin solution. With this technique, the time of spot disappearance is directly proportional to the Sn(II) concentration spotted. The procedure is easy to use, requiring only a high-intensity light source (30-watt light bulb) and a timing device. The test is accurate, reproducible, and sensitive to Sn(II) levels as low as 40 micrograms/ml. Because the procedure is rapid (requiring less than 5 min), it can easily be incorporated into the routine radiopharmaceutical quality-control program of any nuclear medicine facility.

Increased 99mTc-polyphosphate muscle uptake in a patient with polymyositis: case report.

A patient with well-documented rheumatoid arthritis and polymyositis displayed abnormal muscle uptake of 99mTc-polyphosphate during routine bone scanning for occult malignancy. The regions of increased uptake corresponded to the areas of clinically active inflammatory muscle disease. On serial scans the degree of muscle labeling correlated well with both clinical and laboratory indices of disease activity.

A case of myocardial abscess evaluated by radionuclide techniques: case report.

A patient with infective endocarditis was evaluated by Ga-67 citrate imaging, Tc-99m pyrophosphate imaging, equilibrium gated blood pool imaging, and Tl-201 imaging of the chest. The diagnosis of ventricular abscess was first suggested by an abnormal gallium scan. At surgery, an abscess was identified in the area where the scan was abnormal, and postoperatively a repeat scan was normal.

Radioimmunotherapy of patients with cutaneous T-cell lymphoma using an iodine-131-labeled monoclonal antibody: analysis of retreatment following plasmapheresis.

Radioimmunotherapy retreatment of patients receiving radiolabeled murine monoclonal antibodies is difficult because of human antimurine antibody (HAMA) formation. Retreatment therapy was initiated in three patients at the time of disease progression using a radioiodinated monoclonal antibody (T101). The clinical protocol consisted of a two day plasma exchange (4-6 L) to reduce HAMA titers. Immunoimaging was performed with 5 mCi 131I-T101 (10 mg). Gamma scintillation images were obtained 18 hr postinfusion, and radiation dosimetry estimates were performed. At 24 hr postinfusion, each patient received a 100-mCi 131I-T101 (10 mg) therapy dose. Results obtained after plasmapheresis showed a significant reduction, ranging from 28%-61%, in HAMA titers. Blood clearances were markedly different between initial therapy and retreatment therapy for patient with high HAMA titers, reflecting immune complex formation. Two patients responded to retreatment therapy with responses lasting 1 to 2 mo. Minimal acute and no chronic toxicities were observed during the retreatment protocol.

Planar imaging versus gated blood-pool SPECT for the assessment of ventricular performance: a multicenter study.

UNLABELLED: Gated blood-pool SPECT (GBPS), inherently 3-dimensional (3D), has the potential to replace planar equilibrium radionuclide angiography (ERNA) for computation of left ventricular ejection fraction (LVEF), analysis of regional wall motion (RWM), and analysis of right heart function. The purpose of this study was to compare GBPS and ERNA for the assessment of ventricular function in a large, multicenter cohort of patients. METHODS: One hundred seventy-eight patients referred in the usual manner for nuclear medicine studies underwent ERNA followed by GBPS. Each clinical site followed a GBPS acquisition protocol that included 180 degrees rotation, a 64 by 64 matrix, and 64 or 32 views using single- or double-head cameras. Transverse GBPS images were reconstructed with a Butterworth filter (cutoff frequency, 0.45-0.55 Nyquist; order, 7), and short-axis images were created. All GBPS studies were processed with a new GBPS program, and LVEF was computed from the isolated left ventricular chamber and compared with standard ERNA LVEF. Reproducibility of GBPS LVEF was evaluated, and right ventricular ejection fraction (RVEF) was computed in a subset of patients (n = 33). Using GBPS, RWM and image quality from 3D surface-shaded and volume-rendered cine displays were evaluated qualitatively in a subset of patients (n = 30). RESULTS: The correlation between GBPS LVEF and planar LVEF was excellent (r = 0.92). Mean LVEF was 62.2% for GBPS and 54.1% for ERNA. The line of linear regression was GBPS LVEF = (1.04 x ERNA LVEF) + 6.1. Bland-Altman plotting revealed an increasing bias in GBPS LVEF with increasing LVEF (Y = 0.13x + 0.61; r = 0.30; mean difference = 8.1% +/- 7.0%). Interoperator reproducibility of GBPS LVEF was good (r = 0.92). RVEF values averaged 59.8%. RWM assessment using 3D cine display was enhanced in 27% of the studies, equivalent in 67%, and inferior in 7%. CONCLUSION: GBPS LVEF was reproducible and correlated well with planar ERNA. GBPS LVEF values were somewhat higher than planar ERNA, likely because of the exclusion of the left atrium.

Hemophilic bleeding evaluated by blood pool scanning.

The technique of blood pool scanning was used to examine 15 hemophilic subjects. Employing an in vivo method for erythrocyte labeling with Technetium-99 m, a dynamic perfusion sequence is obtained using a scintillation camera positioned over the area to be examined. This demonstrates the vascularity of the tissue. Subsequently, equilibrium blood pool images of the area are obtained and analyzed with a densitometer to assess relative regional blood volume. In patients who were not bleeding but had chronic arthropathy, vascularity was not increased, and the blood volume of comparable joints was similar. By contrast, marked increases in vascularity and image density were observed in studies of acutely bleeding joints. Chronic hemarthroses were associated with persistent, but less marked increases in joint perfusion. Transient increases in joint vascularity were demonstrated after insertion of knee prostheses. In a patient with a thigh hematoma, the dimensions of the hemorrhage were clearly delineated. Since only a tracer dose of nuclide is infused intravenously, there are no allergic reactions or other side effects of the procedure. Blood pool scanning is a safe, non-invasive technique that augments clinical and radiographic evaluations, and provides a new dimension in the assessment of the hemophilic patient.

Usefulness of single-photon emission computed tomography of thallium-201 uptake after dipyridamole infusion for detection of coronary artery disease.

The diagnostic performance of single-photon emission computed tomography (SPECT) and planar imaging of thallium-201 uptake for the detection of coronary artery disease (CAD) was compared in 79 patients who underwent both dipyridamole thallium-201 scintigraphy and coronary angiography. Clinical subgroups were assigned by severity of CAD, presence of a prior myocardial infarction and the number of narrowed coronary arteries. The overall detection of CAD was 89% for SPECT and 67% for planar (p less than 0.001). For the anterior vascular territory, sensitivities for SPECT and planar imaging were 69 and 44% (p less than 0.01), respectively; for the posterior vascular territory, sensitivities were 80 and 54% (p less than 0.01). Receiver-operating characteristic analysis, using a 5-point evaluation scale, was performed for the anterior and posterior vascular territories. Receiver-operating characteristic curves generated for SPECT and planar studies demonstrated improved diagnostic performance by SPECT in the anterior vascular territory, but showed similar performance in the posterior territory because of lower SPECT specificity despite higher sensitivity at clinically relevant decision thresholds. In each clinical subgroup of patients, the detection of CAD by SPECT was significantly superior to that by planar imaging, regardless of the severity of stenosis or the number of significantly narrowed coronary arteries, or whether a myocardial infarction was present. Thus, SPECT thallium-201 scintigraphy is an important and necessary clinical tool for detecting CAD after dipyridamole infusion.

Nuclear medicine imaging workstations based on personal computer technology.

The development of personal computer technology has resulted in extremely powerful, inexpensive computers available as consumer items. With the addition of suitable hardware for gamma camera interfacing and image display, such systems can be transformed into fully functional nuclear medicine computers capable of performing all of the acquisition and processing tasks required in a modern radioisotope imaging department. Such an approach to nuclear medicine computerization offers many advantages in terms of flexibility, speed, cost, and expandability.

Considerations for tomographic imaging of monoclonal antibodies.

Monoclonal antibodies have begun to assume a significant role in clinical research. The ability to label these agents has initiated research in the areas of radioimmunodetection and radioimmunotherapy. In the case of antibodies directed against tumor antigens, imaging has been employed to help assess location and extent of disease, and to provide information and extent of disease, and to provide information concerning biodistribution to be used in subsequent dosimetric calculations. Because of the low counting statistics characteristic of such images, the use of single photon emission computed tomography (SPECT) is suggested as a potential method of improving the diagnostic yield from image data. Careful attention to acquisition parameters and image processing options is needed if these goals are to be achieved.

Safety and efficacy of pantoprazole 40 mg daily as relapse prophylaxis in patients with healed reflux oesophagitis-a 2-year follow-up.

BACKGROUND: Pantoprazole is a benzimidazole derivative which selectively inhibits the proton pump H+, K+-ATPase, necessary for the final step in gastric acid secretion. AIM: To assess safety and efficacy of oral pantoprazole (40 mg o.d.) used as a prophylaxis against relapse in patients with healed reflux oesophagitis during an open-label, 2-year study. METHODS: Outpatients (n=157) with healed stage II or III reflux oesophagitis (Savary-Miller classification) were enrolled into a long-term, multicentre maintenance study. Endoscopy was performed at entry into the study, after 12 and 24 months, or when disease-specific symptoms occurred on more than three consecutive days. Symptoms were assessed at 3-monthly intervals. Endoscopically confirmed relapses (at least stage I) were evaluated as treatment failures. RESULTS: Of the 178 adverse events, experienced by 88 (56%) patients (intention-to-treat population), 12 (7%) were assessed by the investigators as possibly related to the study medication. Median serum gastrin levels increased from a baseline of 46 ng/L to 90 ng/L, reaching a plateau after 9 months. For the intention-to-treat population the endoscopic remission rates after 12 and 24 months were 87% and 76%, respectively (Life-Table survival analysis, Kaplan-Meier). CONCLUSION: Pantoprazole 40 mg proved to be safe and efficacious during a 2-year prophylaxis treatment in patients with healed reflux oesophagitis.

Efficacy and tolerability of pantoprazole 40 mg versus 80 mg in patients with reflux oesophagitis.

BACKGROUND: Pantoprazole is a substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+, K+-ATPase. METHODS: Pantoprazole 40 mg and 80 mg were compared in a randomized double-blind study in 192 out-patients with stage II or III (Savary-Miller classification) reflux oesophagitis. Patients received either pantoprazole 40 mg (n = 97) or pantoprazole 80 mg (n = 95), once daily before breakfast for 4 weeks. Treatment was extended for a further 4 weeks if the oesophagitis had not healed. RESULTS: After 4 weeks complete healing of the reflux oesophagitis was seen in 78% of protocol-correct patients given pantoprazole 40 mg daily (n = 86), and in 72% in the 80 mg (n = 87) group. The cumulative healing rates after 8 weeks were 95 and 94%, respectively (P > 0.05, Cochran-Mantel-Haenszel), and time until healing of oesophagitis comparable in both groups. Differences between doses were also not significant in an intention-to-treat analysis. Both dosing schedules were well tolerated and the patients experienced remarkable symptom relief. No adverse event or changes in laboratory values of clinical significance could definitely be ascribed to the trial medication. CONCLUSION: The 40 mg pantoprazole dosage is comparable to 80 mg in reflux oesophagitis, both in efficacy and tolerability.