Phosphate-32 colloid radiosynovectomy in hemophilia: outcome of 125 procedures.

Radiosynovectomy offers a potentially effective, minimally invasive option for patients with chronic hemarthrosis and synovitis. The long-term outcome of patients with hemophilia who were treated with phosphate-32 chromic phosphate radiosynovectomy was evaluated. One hundred twenty-five procedures in 81 patients were done. Two- to 10-year followup by age and joint included joint bleeding and quality-of-life assessment. In addition, a relative cost comparison, scintigraphic imaging, and evaluation of biodistribution of the radionuclide were done. Of 125 procedures, 54% resulted in complete cessation of bleeding into the treated joint after the procedure, and 73% of patients reported improved mobility of the treated joint. Of patients 18 years old and younger, 79% had a greater than 75% reduction in bleeding incidence, and of patients older than 40 years, only 56% had a similar reduction. Seventy-nine percent of patients surveyed had a significant improvement in quality of life attributable to the treated joint. No evidence of significant leakage was observed. Billing records analysis indicated that radiosynovectomy costs less than 5% of surgical synovectomy. Phosphate-32 chromic phosphate radiosynovectomy is a clinically useful, safe, and cost-effective outpatient procedure in the treatment of patients with chronic hemarthrosis and synovitis.

Inconsistent effects of the proline12 --> alanine variant of the peroxisome proliferator-activated receptor-gamma2 gene on body mass index in children and adolescent girls.

OBJECTIVE: To ascertain whether variation in peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear ligand-dependent transcription factor affecting both adipocyte differentiation and insulin sensitivity, influences body mass index (BMI). DESIGN: Association study. SETTING: Academic research environment. PATIENT(S): Children with premature pubic hair and adolescent girls with hyperandrogenism. INTERVENTION(S): Assay for P12A and P115Q variants and measure BMI. MAIN OUTCOME MEASURE(S): BMI and PPAR-gamma genotypes. RESULT(S): Fourteen subjects were heterozygous for P12A; two were homozygous. None carried the P115Q allele. No significant differences in BMI or basal androstenedione concentrations between P12 carriers and noncarriers were found. Thirty-nine subjects had BMI values at two time points; mean BMI was significantly greater in the P12A carriers at time point 2. Those P12A carriers obese at time point 1 became more obese; lean mutation carriers tended to remain lean. Annual rate of increase in BMI was significantly greater in the P12A carriers than the noncarriers. CONCLUSION(S): Our findings suggest that P12A may be a genetic marker indicating risk for obesity persisting into adolescence. Future studies are needed to determine whether the divergent effects of P12A persist into adulthood, to elucidate the mechanism of this effect, and to replicate our findings in other populations.

32P chromic phosphate radiosynovectomy for chronic haemophilic synovitis.

The principal medical consequence of haemophilia is the development of arthropathy, initiated by a haemarthrosis giving rise to chronic synovitis. Traditional methods of synovectomy include open excision and arthroscopy each of which require substantial amounts of clotting factor concentrate for several weeks, and in the case of open synovectomy, is often associated with loss of range of motion and arthrofibrosis. Radiosynovectomy, the intra-articular injection of low penetration radiocolloids, has been utilized outside the United States for over 20 years. Since 1988, our centre has performed 170 radiosynovectomies utilizing 32P chromic phosphate (32P). This study reports results of 130 32P radiosyovectomies with an average follow-up of 36.5 months (6-140 months). For primary procedures, excellent and good results (haemarthrosis reduction from 75 to 100%) were obtained in 79.2% of cases at 6 months to 8 years. For repeat procedures a combination of excellent and good results were obtained in 62.4% of cases at 6 months to 3 years. Regression analysis showed no correlation between results and age or degree of arthropathy. Radiation was well contained within the joint. There were no observed or identified complications. The procedure is highly cost effective in comparison to open surgical or arthroscopic synovectomy.

Radioiodine dosimetry in patients with end-stage renal disease receiving continuous ambulatory peritoneal dialysis therapy.

In patients with end-stage renal disease (ESRD), Na131I dosages for thyroid cancer may have to be reduced to avoid excess radiation doses to red marrow, because radioiodine is primarily excreted by kidneys. In ESRD patients receiving continuous ambulatory peritoneal dialysis (CAPD) therapy (three to five 2-L exchanges daily) creatinine clearance rates are very low (mean, 7 mL/min), and radioiodine clearance rates may be proportionately reduced. Thus, radioiodine kinetic studies were performed in two hypothyroid CAPD patients with thyroid cancer, in eight euthyroid CAPD patients, and in eight thyroid cancer patients with normal renal function. All received Na131I or Na123I orally, with serial blood, urine, and/or dialysate sampling for 24-70 h. Dosimetry calculations were performed using the MIRDOSE3 computer program. In CAPD patients, serum radioiodine half-times were 5 times longer, and radioiodine clearance rates by urine plus dialysate were 20% of those in patients with normal renal function. Na131I dosages for the two CAPD patients with thyroid cancer were reduced from 150 mCi [5.6 gigabecquerels (GBq)] to 26.6 mCi (0.98 GBq) and 29.9 mCi (1.11 GBq), respectively, resulting in radiation doses to red marrow and total body comparable to those in patients with normal renal function who received a mean of 148 mCi (5.5 GBq) Na131I. Thus, in patients receiving continuous ambulatory peritoneal dialysis therapy, 5-fold reductions in radioiodine clearance rates require 5-fold decreases in Na131I dosages to avoid excessive radiation doses to total body and red marrow.

Radiosynovectomy's clinical applications and cost effectiveness: a review.

It is apparent that from the work of the authors and many others, including the work of Rivard, Sledge, Zuckerman, among others, that radiosynovectomy has an important role to play in providing effective treatment of affected joints associated with rheumatoid arthritis and other forms of arthritis as well as the hemophiliac joint. The treatment offers relief from the effects of recurrent joint effusion with an approximately 60% to 66% favorable response and from recurrent hemarthrosis in the hemophiliac joint with an approximately 75% to 80% favorable response. The impact of providing radiosynovectomy as an alternative to surgical synovectomy is seen, where postoperative side effects such as joint stiffness are avoided, improved quality of life is repeatedly documented, and the cost savings in health care dollars, particularly evident in the hemophiliac joint in this relatively small population, are potentially enormous. With almost two million people in the United States suffering from rheumatoid arthritis, the potential savings in health care dollars is also enormous. As with any use of in vivo radiopharmaceuticals, the potential for radiation-induced damage exists. However, with a 25 plus year record of use, more optimally configured radiopharmaceuticals, and the addition of maneuvers to minimize potential joint leakage, the risk of radiation induced damage appears to be minimal. It appears as though radiosynovectomy is an effective as well as cost-effective alternative to surgical synovectomy and is becoming the procedure of choice particularly in the hemophiliac patient with recurrent hemarthrosis and synovitis who has failed medical therapy. It is also the procedure of choice in patients for whom surgery is contraindicated because of the presence of clotting factor inhibitors.

Cross-linking of Fc gamma receptor IIa and Fc gamma receptor IIIb induces different proadhesive phenotypes on human neutrophils.

Activation of polymorphonuclear leukocytes (PMN) plays an important role in vascular injury associated with systemic vasculitis and in models of autoantibody- and immune complex-mediated disease. The potential role of intravascular activation of PMN, however, is confounded by the observation that some stimuli injected i.v. (e.g., IL-8 and C5a) lead to L-selectin shedding by PMN, which inhibits attachment to endothelium and may be functionally anti-inflammatory. To explore the impact of Fc gamma receptor (Fc gamma R)-mediated activation on the PMN adhesive phenotype, Fc gamma RIIa (CD32) and Fc gamma RIIIb (Cd16) were targeted with receptor-specific reagents, and the expression of adhesion molecules-mediating rolling (L-selectin) and firm adhesion (CD11b/CD18) was measured. Engagement of either Fc gamma RIIa or Fc gamma RIIIb leads to activation, demonstrated by degranulation (upregulation of CD66b), and to increased expression of total CD11b/CD18 and functional CD11b/CD18 (I-domain). In contrast, L-selectin shedding induced by PMN Fc gamma R was divergent. Despite the 5- to 10-fold greater expression and engagement at saturation, activation via Fc gamma RIIIb led to little or no change in L-selectin expression. Stimulation of PMN with intact murine anti-receptor IgG1 showed a contribution of Fc gamma RIIa receptor polymorphisms, underscoring the direct influences of Fc gamma R allotypes on receptor function. These observations suggest that Fc gamma RIIIb-mediated activation of circulating PMN may lead to a proadhesive phenotype likely to promote systemic vascular damage. This Fc gamma R-mediated adhesive phenotype will vary with the receptors engaged and their allotypes, which, in turn, reflect properties of the immune complex and the genetics of the host.

Comparative biodistribution of meta-Tetra(Hydroxyphenyl) chlorin in multiple species: clinical implications for photodynamic therapy.

BACKGROUND AND OBJECTIVE: To optimize photodynamic therapy, it is necessary to know the distribution of photosensitizer in normal tissue as well as tumors and to know how well animal models match human. This study measured the biodistribution of meta-Tetra(Hydroxyphenyl) Chlorin (mTHPC) in three species of animals and in humans. STUDY DESIGN/MATERIALS AND METHODS: mTHPC was injected intravenously into dogs, rabbits, and humans, and drug levels in various tissues were determined 6 days later. One dog was perfused with 3 L of saline to remove blood trapped within organs. RESULTS: Absolute and relative concentrations of drug in specific tissues varied between species and between individuals. There was a general pattern of distribution. Highly vascularized tissues had the highest levels of mTHPC, not simply due to trapping of blood. mTHPC did not localize in bone and did not cross the blood-brain barrier. Humans had much higher levels of drug in their plasma and tissues than did animals. CONCLUSIONS: First, drug retention varies from one tissue to another. Second, there is significant variability from one individual to another, whether animal or human. Third, current models cannot accurately predict from animal studies the optimum dose for humans. Measurement of photosensitizer level in plasma at time of treatment would allow optimal photodynamic dosing.

Technetium-99m-labeled red blood cell scans in the investigation of gastrointestinal bleeding.

PURPOSE: Technetium-99m-labeled red blood cell scans (Tc99m RBC scan) are recommended to confirm gastrointestinal (GI) bleeding. It is controversial whether these scans are sufficient to localize the site of bleeding. This study evaluated the efficacy of RBC scans in confirming and localizing GI bleeding. Our hypothesis was that these scans were effective in localizing GI bleeding if positive within the continuous phase of imaging. METHOD: Tc99m RBC scans were performed on a total of 80 patients over a four-year period to localize GI bleeding (59 male, 21 female; age range 6-88 (mean, 48) years). Films of 75 of the 80 patients were reread by a nuclear medicine physician who was blinded to the original reading and identity and history of the patient. Results of scans were compared with confirmatory studies. RESULTS: A total of 21 patients had positive scans (28 percent). Of these, the site of bleeding in 16 of 21 patients (76 percent) was confirmed by angiography (4/16), endoscopy (10/16), surgery (10/16), or a combination of these. In 14 of the 16 confirmed studies (88 percent), RBC scan correctly localized site of bleeding by our rigid definition. In six patients (4 not confirmed, 2 erroneously localized), scans were positive only at greater than 15 hours. Ten of the 14 correctly localized studies and none of the incorrectly localized studies were positive in the continuous phase of imaging. CONCLUSION: Tc99m RBC scan is effective in localizing GI bleeding when positive within the continuous phase of imaging. In this population supplemental angiography or endoscopy for the purpose of localization would seem unnecessary.

Discrepancies in thyroid uptake values. Use of commercial thyroid probe systems versus scintillation cameras.

This study attempts to find the cause of differences observed between measurements of the thyroid uptake using a thyroid uptake probe and a gamma camera. The thyroid uptakes of 65 patients were measured using the gamma camera with a pinhole collimator and two commercially available thyroid uptake systems. Moreover, simulated thyroid uptake measurements using 0.111 to 7.4 MBq (3 to 200 microCi) of I-123 were also taken using the same probe systems and gamma cameras. Results of the patient and phantom studies were evaluated by regression analyses. The gamma cameras recorded counts in direct proportion to the amount of I-123 in the phantom, but the probe systems exhibited a non-linear relationship. A 20% loss of counts was observed with 1.48 Mq (40 microCi), and up to 50% at the dose relating to a clinically administered dose of 7.4 MBq (200 microCi) in the neck phantom. Because of severe dead-time losses at high count rates associated with counting the capsule standard, the uptake ratios were artifactually higher. The 65 patient study showed a similar trend with the probe technique yielding uptake ratios higher than the gamma camera. Users of thyroid uptake systems should calibrate their instrument's counting efficiency in the dose range of the I-123 activity to be used clinically. To obtain an accurate uptake ratio, the counts must be corrected by calibration factors corresponding to the efficiency of the probe at multiple counting rates including that from counting the intended dose before therapy.

Direct comparison of Tc-99m DTPA and Tc-99m HMPAO for evaluating brain death.

Portable cerebral perfusion studies provide a quick and accurate alternative to traditional confirmatory examinations (such as four-vessel angiography and electroencephalography) to determine brain death. The authors retrospectively analyzed 26 cerebral perfusion studies using both Tc-99m DTPA and Tc-99m HMPAO. The flow agents gave identical results. Additionally, the delayed-phase Tc-99m HMPAO images gave the same results for brain death (14 positive and 12 negative) as the flow images from either agent. Because the Tc-99m HMPAO delayed images can be used for diagnosis, many technical problems become less crucial. Unlike Tc-99m DTPA, Tc-99m HMPAO normally visualizes the gray matter of the cerebellum, midbrain, and medulla. These areas must be evaluated to ensure that they meet the strict criteria for brain death. These differences and the present study suggest that Tc-99m HMPAO is a superior agent for cerebral perfusion studies to determine brain death.

Ga-67 uptake in cutaneous B-cell lymphoma.

Cutaneous B cell lymphoma is not commonly seen and occurs in only 8.2% of non-Hodgkins lymphoma. Although Ga-67 uptake by cutaneous T cell lymphoma has been reported, the literature on Ga imaging in cutaneous, B cell lymphoma is limited. The authors report the gallium scan and clinical findings on 2 cases of cutaneous B cell lymphoma.

Radionuclide imaging in forme fruste of melorheostosis.

Scintigraphy was instrumental in two histologically proven cases of forme fruste melorheostosis. Radionuclide bone scans demonstrated a moderately increased uptake of radiopharmaceutical localized to the "flowing" cortical hyperostosis of melorheostosis observed radiographically. The medullary portion of the affected bones showed no increase in tracer activity. In one case, imaging with Tl-201 chloride demonstrated increased focal activity of the lesion. These scintigraphic findings can help distinguish the mildest manifestation (forme fruste) of melorheostosis from the well-ossified lesions of myositis ossificans and parosteal or periosteal osteosarcoma. The findings of MRI are also described in one patient.

Hemarthrosis and synovitis associated with hemophilia: clinical use of P-32 chromic phosphate synoviorthesis for treatment.

PURPOSE: To evaluate the clinical usefulness of phosphorus-32 chromic phosphate synoviorthesis in patients with hemophilia, recurrent hemarthrosis, and synovitis. MATERIALS AND METHODS: Forty-four P-32 colloid synoviorthesis procedures were performed in 38 patients with these abnormalities. P-32 colloid was injected intramuscularly in a dose of 1.0 mCi (37.0 MBq) in adult knees and 0.5 mCi (18.5 MBq) in adult elbows. A thin-window Geiger-Müller counter was used to survey treated joints, lymph nodes, and liver in order to detect leakage from the joint. Follow-up extended to a maximum of 4 years after treatment. RESULTS: No evidence of clinically significant leakage was seen. Twenty-two of 28 treatments (78%) with longer than 6 months follow-up were associated with improvement in range of motion and frequency of hemorrhage. Of 15 treatments with longer than 2 years follow-up, 10 (67%) were associated with improvement in range of motion; 12 (80%), with improvement in frequency of hemorrhage; and 12 (80%) with improvement in quality-of-life activities. CONCLUSION: P-32 colloid synoviorthesis is a clinically useful out-patient procedure in patients with hemophilia, recurrent hemarthrosis, and synovitis in whom hemostatic therapy has failed.

Osteosarcoma presenting as intestinal obstruction.

Osteosarcoma commonly presents with osseous and pulmonary metastases. We present an unusual case of extraosseous metastatic abdominal chondroblastic osteosarcoma presenting as intestinal obstruction.

Dermatofibrosarcoma protuberans of the toe. Findings on multiple imaging modalities.

Dermatofibrosarcoma protuberans occurs early in life, is an unusual soft tissue tumor, and is uncommonly seen distal to knees. The authors present a rare case of dermatofibrosarcoma protuberans of the toe with different imaging modalities.

The evaluation of 186Re-labeled antibodies using N2S4 chelate in vitro and in vivo using tumor-bearing nude mice.

We have recently described a method for radiolabeling monoclonal antibodies, with metallic radionuclides using a new chelating agent N2S3. Using this chelate the monoclonal antibodies Lym-1 and B72.3 were labeled with 186Re and their biological integrity was evaluated in vitro and in vivo. 186Re-labeled antibodies using N2S4 methodology were found to be stable in human serum and retained their immunoreactivity. Intravenous administration of 0.5 mCi 186Re-labeled antibodies resulted in partial or complete regression of tumor tissue in mice.

Synthesis and preliminary evaluation of a new chelate N2S4 for use in labeling proteins with metallic radionuclides.

The successful attachment of various metallic radionuclides such as 99mTc to monoclonal antibodies for targeting tumor tissue in vivo depends upon the development and use of suitable bifunctional chelating agents. We have successfully synthesized a new N2S4 (compound 4) chelate. This chelate forms a stable complex with 99mTc and is capable of coupling to different proteins. The N2S4 compound is quite stable if kept as a hydrochloride salt and is coupled to antibody under neutral conditions with better than 95% efficiency without the loss of immunoreactivity.