Development of a simple and selective separation of 67Cu from irradiated zinc for use in antibody labelling: a comparison of methods.

A procedure for the production and separation of Cu isotopes from irradiated Zn was developed. Following a comparison of methods based on extraction, electrolysis and ion-exchange chromatography, a technique for the separation of Cu employing three ion-exchange matrices was developed which was simple, reproducible and hot cell-compatible. The specific activity of the final product was 37 MBq 67Cu/microgram Cu at EOB. The level of impurities was so low that no interference with antibody labelling was observed.

Cellular processing of copper-67-labeled monoclonal antibody chCE7 by human neuroblastoma cells.

Monoclonal antibody chCE7, an internalizing neuroblastoma-specific chimeric antibody, was derivatized with the macrocyclic amine ligand 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)-methyl] benzoic acid tetrahydrochloride and labeled with the potential therapeutic nuclide 67Cu. Using pulse labeling and an acid elution endocytosis assay, 67Cu-chCE7 was found to be internalized into human neuroblastoma (SKN-AS) cells at a similar rate and to a similar extent as 125I-labeled chCE7. Uptake of 67Cu-chCE7 and 125I-chCE7 into the acid stable (intracellular) pool proceeded with similar kinetics during the first 2 h of internalization. However, in contrast to 125I-chCE7-loaded cells, at later times intracellular radioactivity kept increasing in the case of 67Cu-chCE7-loaded cells. It was shown that this effect is due to the intracellular accumulation of a low M(r) degradation product consisting of the 67Cu-4[(1,4,8,11-tetraazacyclotetradec-1-yl)-methyl] benzoic acid complex, possibly with a short peptide attached to it. Degradation of both 125I-chCE7 and 67Cu-chCE7 was inhibited by chloroquine, indicating endosomal or lysosomal degradation, and a 43,000 M(r) fragment was found to be the major high M(r) degradation product in both cases. Although at times between 4 and 6 h of internalization intracellular breakdown of 67Cu-chCE7 was found to proceed more slowly, the major difference between the two immunoconjugates resides in the prolonged cellular retention of the 67Cu-chCE7 metabolite.

Blood to brain iron uptake in one rhesus monkey using [Fe-52]-citrate and positron emission tomography (PET): influence of haloperidol.

Iron is highly concentrated in the basal ganglia of the brain. The involvement of cerebral iron and its handling systems in neurodegenerative brain diseases like Parkinson's disease and tardive dyskinesia is currently under close investigation. There is evidence from animal studies that neuroleptics can increase iron uptake into brain. This effect appeared to be due to alteration of blood-brain barrier transport by the neuroleptics, particularly chlorpromazine and haloperidol, but not clozapine. We have investigated one Rhesus monkey using positron emission tomography (PET) and [Fe-52]-citrate before and during haloperidol administration. After drug withdrawal during a period of 1.5 year the investigation procedure was repeated. The results show that in the investigated monkey haloperidol induces a reversible marked increase of iron transport across the blood brain barrier concomitant with a large increase in elimination rate of the tracer from the blood.

Efficacy of adenoidectomy for recurrent otitis media in children previously treated with tympanostomy-tube placement. Results of parallel randomized and nonrandomized trials.

We studied the efficacy of adenoidectomy in 213 children who had received tympanostomy-tube placement because of persistent and/or recurrent otitis media and had again developed otitis media after tubal extrusion. Ninety-nine of the children were assigned randomly to either an adenoidectomy group or a control group; in a separate trial, 114 children whose parents withheld consent for randomization were assigned according to parental preference. In both trials, control group outcomes appeared to have been biased favorably by the withdrawal of certain severely affected subjects from control status to receive adenoidectomy. Nonetheless, in both trials, adenoidectomy group outcomes were more favorable than control group outcomes during the first 2 follow-up years. Statistically significant differences were found mainly in the randomized trial, where during the first and second years, respectively, adenoidectomy subjects had 47% and 37% less time with otitis media than control subjects and 28% and 35% fewer suppurative (acute) episodes than control subjects. We conclude that adenoidectomy is warranted on an individualized basis for children who develop recurrent otitis media after extrusion of tympanostomy tubes.

Efficacy of tonsillectomy for recurrent throat infection in severely affected children. Results of parallel randomized and nonrandomized clinical trials.

We studied the efficacy of tonsillectomy, or tonsillectomy with adenoidectomy, in 187 children severely affected with recurrent throat infection. Ninety-one of the children were assigned randomly to either surgical or nonsurgical treatment groups, and 96 were assigned according to parental preference. In both the randomized and nonrandomized trials, the effects of tonsillectomy and of tonsillectomy with adenoidectomy were similar. By various measures, the incidence of throat infection during the first two years of follow-up was significantly lower (P less than or equal to 0.05) in the surgical groups than in the corresponding nonsurgical groups. Third-year differences, although in most cases not significant, also consistently favored the surgical groups. On the other hand, in each follow-up year many subjects in the nonsurgical groups had fewer than three episodes of infection, and most episodes among subjects in the nonsurgical groups were mild. Of the 95 subjects treated with surgery, 13 (14 per cent) had surgery-related complications, all of which were readily managed or self-limited. These results warrant the election of tonsillectomy for children meeting the trials' stringent eligibility criteria, but also provide support for nonsurgical management. Treatment for such children must therefore be individualized.

Functional and morphological alterations of the exocrine pancreas in the rat following pretreatment with rifampicin.

Following oral pretreatment with rifampicin over 3 and 9 days, the exocrine pancreatic function was studied in urethane-anaesthetized rats under exocrine stimulation. The volume and electrolyte content, and especially the protein and amylase outputs of the pancreatic secretion showed a virtually dose- and time-dependent decrease. Histologically, there was a corresponding decline of the zymogen granules in the acinar cells. The suggested explanation for the observed disorders of the pancreatic exocrine function is primarily an inhibition of protein synthesis due to rifampicin.

History of recurrent sore throat as an indication for tonsillectomy. Predictive limitations of histories that are undocumented.

As part of a prospective study of indications for tonsillectomy and adenoidectomy, we followed closely 65 children with histories of recurrent throat infection that seemed impressive (at least seven episodes in one year, five in each of two consecutive years or three in each of three consecutive years), but lacked documentation. During the first year of observation, only 11 children (17 per cent) had episodes of throat infection with clinical features and patterns of frequency conforming to those described in their presenting histories. Of the remaining 54 children, 43 (80 per cent) experienced no, one or two observed episodes each, and most of the episodes were mild. We conclude that undocumented histories of recurrent throat infection do not validly forecast subsequent experience and hence do not constitute an adequate basis for subjecting children to tonsillectomy.