Myeloablative 131I-tositumomab radioimmunotherapy in treating non-Hodgkin's lymphoma: comparison of dosimetry based on whole-body retention and dose to critical organ receiving the highest dose.

Myeloablative radioimmunotherapy using (131)I-tositumomab (anti-CD20) monoclonal antibodies is an effective therapy for B-cell non-Hodgkin's lymphoma. The amount of radioactivity for radioimmunotherapy may be determined by several methods, including those based on whole-body retention and on dose to a limiting normal organ. The goal of each approach is to deliver maximal myeloablative amounts of radioactivity within the tolerance of critical normal organs. METHODS: Records of 100 consecutive patients who underwent biodistribution and dosimetry evaluation after tracer infusion of (131)I-tositumomab before radioimmunotherapy were reviewed. We assessed organ and tissue activities over time by serial gamma-camera imaging to calculate radiation-absorbed doses. Organ volumes were determined from CT scans for organ-specific dosimetry. These dose estimates helped us to determine therapy on the basis of projected dose to the critical normal organ receiving a maximum tolerable radiation dose. We compared organ-specific dosimetry for treatment planning with the whole-body dose-assessment method by retrospectively analyzing the differences in projected organ-absorbed doses and their ratios. RESULTS: Mean organ doses per unit of administered activity (mGy/MBq) estimated by both methods were 0.33 for liver and 0.33 for lungs by the whole-body method and 1.52 for liver and 1.74 for lungs by the organ-specific method (P=0.0001). The median differences between methods were 0.92 mGy/MBq (range, 0.36-2.2 mGy/MBq) for lungs, 0.82 mGy/MBq (range, 0.28-1.67 mGy/MBq) for liver, and -0.01 mGy/MBq (range, -0.18-0.16 mGy/MBq) for whole body. The median ratios of the treatment activities based on limiting normal-organ dose were 5.12 (range, 2.33-10.01) for lungs, 4.14 (range, 2.16-6.67) for liver, and 0.94 (range, 0.79-1.22) for whole body. We found substantial differences between the dose estimated by the 2 methods for liver and lungs (P=0.0001). CONCLUSION: Dosimetry based on whole-body retention will underestimate the organ doses, and a preferable approach is to evaluate organ-specific doses by accounting for actual radionuclide biodistribution. Myeloablative treatments based on the latter approach allow administration of the maximum amount of radioactivity while minimizing toxicity.     

A novel mutation in the last exon of ATRX in a patient with α-thalassemia myelodysplastic syndrome

Abstract:  We describe a patient with acquired alpha-thalassemia myelodysplastic syndrome (ATMDS). A previously healthy 66-year-old man presented with hemoglobin of 9.3 g/dL, mean corpuscular volume 59 fL, and a bone marrow aspirate with increased erythroid precursors and hypolobulated megakaryocytes. Hemoglobin H inclusions were seen in most red cells after 1% brilliant cresyl blue supravital stain of the peripheral blood. At the molecular level, we identified of a novel mutation in the most 3' exon of the ATRX gene ( C GA→ T GA substitution in codon 2407) resulting in a premature termination codon (p.R2407X). This case provides further evidence for a link between ATRX mutations and ATMDS, and suggests a possible role for the conserved Q-box element in ATRX function.     

Ultrastructural alterations in caudate nucleus in aged cats

These studies provide information on the changes in the ultrastructure in the caudate nucleus of aged cats. The major findings was that there was a decrease in the density of synapses in caudate neuropil. This decrease occurred in animals after 3 years of age and remained relatively constant in older animals. In conjunction with this change a population of unusually long synapses also occurred. These larger synaptic appositions were associated with enlarged spine heads. The caudate also showed a number of qualitative ultrastructural alterations. Many neurons contained accumulations of lipofuscin or lipopigment granules in aged animals. These inclusions occurred in both soma and dendrites of neurons and all types of glial cells. A unique configuration of collapsed agranular cisterns also was observed in aged animals. The present results indicate that decreases in synaptic density may by one morphological event underlying functional alterations observed in caudate neurons in aged cats.     

Gastric Bypass for Morbid Obesity: a Standard Surgical Technique by Consensus

Background: The gastric bypass operation has evolved since 1966 when it was first introduced. The purpose of this study was to determine the present state of gastric bypass by consensus among the members of the American Society for Bariatric Surgery (ASBS). Method: A questionnaire was sent to all members of the ASBS. Forty-three percent responded reporting over 41,200 cases. Results: Results were analyzed by using χ² tests with a null hypothesis. Surgeons agreed on several technical aspects, preferring a vertical to a horizontal stapleline; estimating, rather than measuring, the pouch volume at an average of 22 cc. Few surgeons divide the short gastric vessels, and only 25% of surgeons polled use a restrictive ring or band proximal to the gastroenterostomy. Most surgeons calibrate the gastroenterostomy, reporting a preferred average diameter of 12.3 cm. There was no consensus regarding forming the gastroenterostomy, 58% preferring hand-sewn and 42% stapled anastomoses. There was no consensus regarding dividing the gastric pouch from the bypassed stomach: Conclusion: The preferred gastric bypass is vertical, with the pouch estimated at 20-25 cc, and the gastroenterostomy calibrated at 12 mm diameter. The short gastric vessels need not be divided, and restrictive bands or rings are not preferred. This technique of gastric bypass should be used as the control procedure when modifications are tested in future trials. Randomized prospective studies are suggested to probe the benefits of division of the stomach pouch from the bypassed stomach.     

Accommodative hysteresis under static and dynamic stimulus conditions

The influence of continuous variation in dioptric demand on the accommodative hysteresis induced at near distances was examined in 14 visually-normal young adults. Tonic accommodation was measured before and after 10 minutes of sustained focus using a constant stimulus at 5 D, 6.5 D, and 8 D, as well as a stimulus which slowly and alternately increased and decreased over the continuous range from 5 D to 8 D. For approximately half the subjects, dioptric demand had to be very high (8 D) under static conditions to produce moderate but significant hysteresis, yet little or no attenuation of the effect occurred under the dynamic condition. For other subjects who consistently showed very large tonic changes (1.4 D or more) under static conditions, the hysteresis effect generated under dynamic conditions was greatly reduced (approximately 50 per cent) in magnitude. These findings suggest that the degree to which continuous variation in dioptric demand will disrupt the adaptive process may depend on individual differences in the rate and/or maximum level of tonic accommodative change. Such a relationship could have bearing on the particular strategy recommended for individuals who tend to experience blur at distance following nearwork.     

Joint action between binary mixtures of chlordimeform and insecticides.

Chlordimeform (CDF) was tested for its ability to act jointly with an organophosphorus insecticide (parathion) and a series of carbamate insecticides. Three arthropod species were used as test subjects: the two-spotted spider mite, Tetranychus urticae; the German cockroach, Blatella germanica; and the flour beetle, Tenebrio castaneum. However, CDF antagonized the toxicity of parathion toward B. germanica while it acted in a greater than additive fashion toward T. castaneum. No combination of CDF and insecticide tested acted jointly toward T. urticae. Species-specific differences in sensitivity, absorption, metabolism, and mode of delivery account for the varying results. Metabolic studies of pairs of compounds using two radiolabeled carbamates showed that CDF altered the metabolic detoxification of both carbaryl and aldicarb. The results suggest that CDF may inhibit MFOs as its mode of action.