Buffering and dilution in red blood cell storage.

BACKGROUND: Red blood cell (RBC) storage solutions work in a narrow pH range between 7.2 and 6.4. While keeping RBC within that pH range, ATP production can be increased by buffering or dilution. STUDY DESIGN AND METHODS: In the first study, 12 units of packed CP2D RBCs were pooled in groups of four, re-aliquoted, and added to one of four additive solutions (ASs): AS-3, 110 mL; EAS-61, 170 mL; EAS-78, 170 mL; or EAS-81, 110 mL. EAS-78 and -81 contain bicarbonate. Units were sampled approximately weekly for 10 weeks for biochemical measures. In the second study, 12 volunteers donated RBCs for measures of (51)Cr in vivo recovery after 6 or 8 weeks of storage in EAS-81. RESULTS: RBCs stored in the higher-volume or buffered ASs had higher RBC ATP concentrations. The combination had an additive effect. Hemolysis was reduced in dilute ASs and less so with buffering. RBCs stored for 8 weeks (n=6) in EAS-81 exhibited 87+/- 2 percent 24-hour (51)Cr in vivo recovery and 0.4+/- 0.2 percent hemolysis. CONCLUSIONS: It is possible to store RBCs for 8 weeks in buffered conventional volume ASs. Combining buffering and increased AS volume improves stored RBC characteristics further.

Painful osteoblastic metastases: the role of nuclear medicine.

Although bone pain from osteoblastic metastases can be ameliorated 50% to 80% of the time by use of intravenously or orally administered radiopharmaceuticals, we cannot accurately predict who will or will not respond. The radiopharmaceuticals containing phosphorus-32, strontium-89 (Metastron), rhenium-186, samarium-153 lexidronam (Quadramet), and tin-117m are effective, but we do not know which of these is the most efficacious or the safest. Toxicity includes mild-to-moderate pancytopenia and an occasional brief flare of pain, and treatment of patients with disseminated intravascular coagulation must be avoided because it may predispose the patient to severe thrombocytopenia. Treatment may be repeated at approximately 8- to 12-week intervals, depending on the time of return to normal leukocytes and platelet counts. Tumoricidal effects are probably not the sole mechanism of pain relief.

RBC storage for 11 weeks.

BACKGROUND: Increasing the length of RBC storage can increase both RBC availability and quality. This work addresses 11-week RBC storage in experimental ASs (EASs). STUDY DESIGN AND METHODS: Three studies were performed. In the first, 24-hour in vivo recovery of (51)Cr-labeled autologous RBCs was measured in nine volunteers after storage of their RBCs for 11 weeks in EAS 67. In the second study, 4 units of blood were divided and stored in aliquots with an EAS containing 0, 15, 30, or 45 mmol per L of mannitol; then hemolysis, RBC morphology, and microvesicle protein were measured. In the third study, 6 full units were stored for 12 weeks in the EAS containing 30 mmol per L of mannitol, with weekly sampling for morphologic and biochemical measures of RBC quality. RESULTS: RBCs stored for 11 weeks in EAS-67 had a mean 24-hour in vivo recovery of 79 +/- 5 percent, but the hemolysis was 1.35 +/- 0.68 percent. Increasing mannitol content of the EAS reduced hemolysis but increased microvesiculation. EAS-76, with 30 mmol per L of mannitol allowed 11-week storage with 0.48 +/- 0.10 percent hemolysis at 11 weeks and 0.62 +/- 0.14 percent hemolysis at 12 weeks. CONCLUSION: It is possible to store RBCs for 11 weeks in EAS with greater than 75 percent recovery and less than 1 percent hemolysis.

Therapeutic 131I in outpatients: a simplified method conforming to the Code of Federal Regulations, title 10, part 35.75.

UNLABELLED: The Code of Federal Regulations, title 10, part 35.75 (10CFR35.75), provides greater latitude and flexibility in the dosing and management of outpatients treated with therapeutic 131I than did preceding regulations. Prescribing physicians should consider applying these new regulations to enhance patient convenience and lower the cost of managing appropriate outpatients. Managed care organizations and third-party payers may require that all eligible patients be treated as outpatients or that justification for hospital admission be specifically documented. To facilitate application of the code and guidelines, maximum 131I doses for patients undergoing thyroid remnant ablation, therapy for metastatic or recurrent thyroid cancer, or therapy for hyperthyroidism have been calculated and summarized in tables. METHODS: A model was developed that calculates the maximum dose of 131I that may be dispensed to an outpatient. This model complies with 10CFR35.75. The maximum dose is calculated as a function of 5 variables: the occupancy factors for 3 periods after dose administration, the fractional uptake of 131I by residual thyroid tissue or metastasis, and the duration of constrained activity. Occupancy factor, a key new concept in the regulatory guidelines, is a physician estimate of the time that a treated patient will be near the individual with whom the patient will spend the most time after treatment. The model also considers 3 constants: the effective half-life of 131I during the preequilibrium period, and the effective half-lives of 131I in both the thyroidal component and the extrathyroidal component during the equilibrium period. Tables for maximum allowable patient 131I doses were derived on the basis of this model. RESULTS: Through dosing charts, maximum 131I therapy doses may easily be calculated. Most outpatients undergoing thyroid remnant ablation, therapy for metastatic or recurrent thyroid cancer, or therapy for hyperthyroidism may be treated with 7400 MBq (200 mCi) 131I or more. CONCLUSION: If the prescribing physician understands the concept of occupancy factor and how to use the dosing charts, our model facilitates application of and adherence to 10CFR35.75.

Systemic radiopharmaceutical therapy of painful osteoblastic metastases.

Bone pain from osteoblastic metastases can be ameliorated 40% to 80% of the time. Although we can predict nonresponders, we cannot predict responders; however, patients with a better performance scale may have a better chance of pain relief. Radiopharmaceuticals containing phosphorus 32, strontium 89, samarium 153, rhenium 186, and tin 117m are effective, but we do not know which is the most efficacious and the safest. Toxicity includes the flare phenomenon and mild to moderate pancytopenia, but disseminated intravascular coagulation can cause severe, life-threatening thrombocytopenia. This treatment may be repeated at about 9- to 12-week intervals, perhaps earlier with (153)Sm lexidronam, (186)Re etidronate, and (117m)Sn pentetate, with a success rate approaching that of the initial injection. The duration of action of pain reduction ranges from 2 weeks to many months. Tumorical effects are probably not the only mechanism of pain relief.

Trends in American nuclear medicine training: past, present, and future.

As soon as the capability to produce radioactive atoms was achieved in the 1930s, physician-scientists gravitated as apprentices toward important research centers, such as those at Berkeley, Washington University, and Massachusetts Institute of Technology (M.I.T.)/Massachusetts General Hospital. After World War II, Oak Ridge Associated Universities (ORAU) trained many of the founders of the specialty of nuclear medicine. The initial ORAU preparatory course lasted only 3 weeks. Over the 20 years after World War II, only 100 to 200 physicians had learned radioisotopic techniques and their clinical applications from their older preceptors. The founding of the conjoint American Board of Nuclear Medicine in 1971 (cosponsored by the American Boards of Internal Medicine, Pathology, and Radiology) marked a new era in certifying the quality of graduates of a growing number of nuclear medicine residency programs. Future trends in nuclear medicine education include the following: greater availability of jobs for physicians with board certification in radiology and nuclear medicine; an increased emphasis on training in positron-emission tomography (PET); and recertification and documentation of maintenance of professional competence as certainties.

Successful storage of RBCs for 9 weeks in a new additive solution.

BACKGROUND: This study explored the effect of storing packed RBCs suspended in 200 mL of an alkaline, hypotonic, experimental additive solution (EAS 61). STUDY DESIGN AND METHODS: Packed RBC units prepared from RBCs collected from healthy donors in CPD were stored for 8 (n = 10) and 9 (n = 10) weeks under blood bank conditions after the addition of 200 mL of EAS 61 (adenine, 2 mM:; dextrose, 110 mM:; mannitol, 55 mM:; NaCl, 26 mM:; Na(2)HPO(4), 12 mM:). Standard methods were used for in vitro assays. The 24-hour in vivo autologous recoveries were measured with (51)Cr. RESULTS: Mean +/- SD recoveries at 8 and 9 weeks were 81 +/- 7 and 77 +/- 7 percent. After 9 weeks, the ATP of the RBCs was 81 percent of the initial value, hemolysis was 0.35 percent, supernatant potassium was 46 mEq per L, and the morphologic index was 94.1. CONCLUSION: Packed RBCs suspended in 200 mL of EAS 61 can be stored satisfactorily for 9 weeks. Longer RBC storage should reduce outdating, increase availability of transfusions in remote locations, and improve the efficiency of autologous donor programs.

Successful storage of RBCs for 10 weeks in a new additive solution.

BACKGROUND: The effect of storing packed RBCs suspended in 300 mL of an alkaline, experimental additive solution (EAS 64) was explored. STUDY DESIGN AND METHODS: RBC units prepared from blood collected from healthy donors into CPD were WBC reduced and stored for 10 weeks under blood bank conditions after the addition of 300 mL of EAS 64 (adenine, 2 mM:; dextrose, 50 mM:; mannitol, 20 mM:; NaCl, 75 mM:; Na(2)HPO(4), 9 mM:). For comparison, non-WBC-reduced units from the same donors were stored in a different additive solution (AS-1, Baxter Healthcare) for 6 weeks. Standard methods were used for the in vitro assays. The 24-hour in vivo recoveries were measured by using (51)Cr- and (99m)Tc-labeled RBCs. RESULTS: Mean recovery in the EAS 64 units after 10 weeks was 84 +/- 8 percent, the same as in the AS-1 units stored for 6 weeks. For EAS 64 and AS-1 units, respectively, the ATP of the RBCs was 85 percent and 64 percent of the initial value, hemolysis was 0.43 percent and 0.63 percent, supernatant potassium was 24 mEq per L and 44 mEq per L, and the morphologic index was 98 and 71. CONCLUSION: RBCs suspended in 300 mL of EAS 64 can be stored satisfactorily for 10 weeks. Longer RBC storage should reduce outdating, increase availability of transfusions in remote locations, and improve the efficiency of autologous donor programs.

A case of elevated spontaneous micronucleus frequency derived from chromosome 2.

This work tested the hypothesis that the content of spontaneous micronuclei in lymphocytes in an apparently healthy normal human subject, who exhibited an unusually high micronucleus frequency, was non-random. Several DNA probes were used in fluorescent in-situ hybridization (FISH), beginning with a probe generated from the subject's micronuclei. Micronuclei obtained from peripheral blood lymphocytes by microdissection were subjected to random amplification of polymorphic DNA (RAPD-PCR), and a unique PCR product was then used to isolate a cosmid clone from a human genomic library. This clone hybridized to chromosome 2. Subsequently, commercial probes were included in FISH analyses of micronuclei from the subject and age- and sex-matched controls. No significant differences were found between subject and controls in the percentages of micronuclei hybridizing with a centromere probe for the X chromosome or a painting probe for chromosome 3. However, the subject had a very highly significant increase (p<0.0001) in chromosome 2 in micronuclei over a level that might be expected to be present by chance. Characterization of micronuclei may be a promising tool in studies of mechanisms of inherited or induced chromosome instability. The strength of the strategy employed in this study is that, by characterizing the chromosomes present in micronuclei, this work has advanced from an observation of chromosomal instability to a foundation for study of the mechanism underlying the observation.

Prevalence of adverse reactions to positron emitting radiopharmaceuticals in nuclear medicine. Pharmacopeia Committee of the Society of Nuclear Medicine.

UNLABELLED: This study was undertaken to determine the prevalence of adverse reactions to positron emitting radiopharmaceuticals as well as to nonradioactive drugs used in interventional nuclear medicine during PET studies. METHODS: A prospective 4-yr study was performed with 22 collaborating institutions using a questionnaire, which indicated for each month of the study the number of PET procedures performed, the number of adverse reactions to PET radiopharmaceuticals as well as the number of adverse reactions to interventional nonradioactive pharmaceuticals used for PET. RESULTS: A total of 33,925 radiopharmaceutical doses were recorded in a retrospective examination of records by the 22 participating institutions. In addition, the total prospective number of administered doses recorded by the participants was 47,876, for a total number of positron emitting radiopharmaceutical administrations of 81,801. No adverse reactions were found from any PET radiopharmaceutical dose. There were no deaths or hospitalizations caused by nonradioactive interventional pharmaceuticals used adjunctive to PET studies. CONCLUSION: PET radiopharmaceuticals have an extraordinary safety record with no adverse reactions reported in over 80,000 administered doses in this study.

Time-dependent changes in the density and hemoglobin F content of biotin-labeled sickle cells.

Sickle red blood cells (RBC) are subject to a number of important cellular changes and selection pressures. In this study, we validated a biotin RBC label by comparison to the standard 51Cr label, and used it to study changes that occur in sickle cells as they age. Sickle RBC had a much shorter lifespan than normal RBC, but the two labels gave equivalent results for each cell type. A variable number of sickle, but not normal, RBC disappeared from the circulation during the first few hours after reinfusion. The number of biotinylated sickle reticulocytes was decreased by 50% after 24 h and 75% after 48 h, with a gradual decrease in the amount of reticulum per cell. The labeled sickle cells exhibited major density increases during the first 4-6 d after reinfusion, with smaller changes thereafter. A small population of very light, labeled sickle RBC was essentially constant in number after the first few days. Fetal hemoglobin (HbF) content was determined in isolated biotinylated sickle RBC after reinfusion, allowing an estimate of lifespan for RBC containing HbF (F cells) and non-F cells. The lifespan of sickle biotinylated RBC lacking HbF was estimated to be approximately 2 wk, whereas F cells survived 6-8 wk.

Treatment of metastatic bone pain with tin-117m Stannic diethylenetriaminepentaacetic acid: a phase I/II clinical study.

The physical characteristics of Sn-117m combined with the biodistribution of the compound tin-117m (Stannic, 4+) diethylenetriaminepentaacetic acid (Sn-117m DTPA) suggest that it should be an excellent agent for the palliation of pain from bony metastases. Prior work has established the dosimetry and the safety for the material in human beings. The presence of low-energy conversion electrons should result in the relative sparing of the bone marrow while delivering a high radiation dose to sites of bony metastatic disease. Forty-seven patients with painful bone metastases from various malignancies were treated with Sn-117m DTPA. The patients were assigned to five different dose levels ranging from 2.64 to 10.58 MBq (71-286 microCi) per kg of body weight. Follow-up included review of pain diaries, performance scores, analgesic requirements, blood chemistries, and hematological assessment. Three patients received a second treatment. There was an overall response rate for relief of pain of 75% (range, 60-83%) in the 40 treatments that could be evaluated. No correlation was apparent in this limited series between response rate and the five dose levels used. The relief was complete in 12 patients (30%). The time to onset of pain relief was 19 +/- 15 days with doses < or = 5.29 MBq/kg and 5 +/- 3 days with doses > or = 6.61 MBq/kg. Myelotoxicity was minimal, with only one patient having a marginal grade 3 WBC toxicity. On the basis of our data, Sn-117m DTPA should be an effective and safe radiopharmaceutical for palliation of painful bony metastases. A large-scale trial is warranted to evaluate it in comparison to other similar agents.

Calculating lens dose and surface dose rates from 90Sr ophthalmic applicators using Monte Carlo modeling.

Using a 90Sr applicator for brachytherapy for the reduction of recurrence rates after pterygium excisions has been an effective therapeutic procedure. Accurate knowledge of the dose being applied to the affected area on the sclera has been lacking, and for decades inaccurate estimates for lens dose have thus been made. Small errors in the assumptions which are required to make these estimates lead to dose rates changing exponentially because of the attenuation of beta particles. Monte Carlo simulations have been used to evaluate the assumptions that are now being used for the calculation of the surface dose rate and the corresponding determination of lens dose. For an ideal 90Sr applicator, results from this study indicate dose rates to the most radiosensitive areas of the lens ranging from 8.8 to 15.5 cGy/s. This range is based on different eye dimensions that ultimately corresponds to a range in distance between the applicator surface and the germinative epithelium of the lens of 2-3 mm. Furthermore, the conventional 200 cGy threshold for whole lens cataractogenesis is questioned for predicting complications from scleral brachytherapy. The dose to the germinative epithelium should be used for studying radiocataractogenesis.