166Ho-DOTMP radiation-absorbed dose estimation for skeletal targeted radiotherapy.

166Ho-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate (DOTMP) is a tetraphosphonate molecule radiolabeled with 166Ho that localizes to bone surfaces. This study evaluated pharmacokinetics and radiation-absorbed dose to all organs from this beta-emitting radiopharmaceutical. METHODS: After two 1.1-GBq administrations of 166Ho-DOTMP, data from whole-body counting using a gamma-camera or uptake probe were assessed for reproducibility of whole-body retention in 12 patients with multiple myeloma. The radiation-absorbed dose to normal organs was estimated using MIRD methodology, applying residence times and S values for 166Ho. Marrow dose was estimated from measured activity retained after 18 h. The activity to deliver a therapeutic dose of 25 Gy to the marrow was determined. Methods based on region-of-interest (ROI) and whole-body clearance were evaluated to estimate kidney activity, because the radiotracer is rapidly excreted in the urine. The dose to the surface of the bladder wall was estimated using a dynamic bladder model. RESULTS: In clinical practice, gamma-camera methods were more reliable than uptake probe-based methods for whole-body counting. The intrapatient variability of dose calculations was less than 10% between the 2 tracer studies. Skeletal uptake of 166Ho-DOTMP varied from 19% to 39% (mean, 28%). The activity of 166Ho prescribed for therapy ranged from 38 to 67 GBq (1,030-1,810 mCi). After high-dose therapy, the estimates of absorbed dose to the kidney varied from 1.6 to 4 Gy using the whole-body clearance-based method and from 8.3 to 17.3 Gy using the ROI-based method. Bladder dose ranged from 10 to 20 Gy, bone surface dose ranged from 39 to 57 Gy, and doses to other organs were less than 2 Gy for all patients. Repetitive administration had no impact on tracer biodistribution, pharmacokinetics, or organ dose. CONCLUSION: Pharmacokinetics analysis validated gamma-camera whole-body counting of 166Ho as an appropriate approach to assess clearance and to estimate radiation-absorbed dose to normal organs except the kidneys. Quantitative gamma-camera imaging is difficult and requires scatter subtraction because of the multiple energy emissions of 166Ho. Kidney dose estimates were approximately 5-fold higher when the ROI-based method was used rather than the clearance-based model, and neither appeared reliable. In future clinical trials with 166Ho-DOTMP, we recommend that dose estimation based on the methods described here be used for all organs except the kidneys. Assumptions for the kidney dose require further evaluation.     

The role of microsomal oxidation processes in the development of haloperidol tolerance during melatonin administration and epiphysectomy in rats

A pineal hormone melatonin (1 mg/kg, 24 days) facilitated the formation of tolerance to haloperidol and eliminated the changes produced by it in the processes of microsomal oxidation in rats. Pinealectomy yielded the opposite result. After pinealectomy the normalizing effect of the hormone on the condition of the liver monoxygenase system and the effects of haloperidol weakened.     

Dentists evaluate their patients: An empirical investigation of preferences

Dental treatment is a dyadic encounter. Yet research on the dentist-patient dyad has tended to focus on patient perceptions of dentist, to the neglect of dentist perceptions of patient. Previous theoretic and qualitative work on caregiver perceptions of patients suggested three dimensions of evaluation. Dentists (N=618) rated their patients on items taken from two prior studies. Dentists' responses were subjected to confirmatory factor analysis. The analysis substantiated the existence of three evaluative dimensions: compliance, tractability, and likability. Further analysis showed that the three dimensions formed a Guttman simplex, revealing a second-order factor of selectivity and allowing a classification of dentists on the basis of patient selectivity.This study was funded by a grant from the University of Connecticut Research Foundation.     

Dermatomyositis and miliary tuberculosis (case report with fatal outcome )

A 50-year old female patient suffering from dermatomyositis, who had undergone thymectomy, died of generalized miliary tuberculosis.     

Endoscopic removal of isolated gastrinoma of the duodenum after Billroth II gastric resection]

Duodenal carcinoma is a rare disease and is encountered in no more than 10% of cases of the Zollinger-Ellison syndrome. The article discusses a rare case in which an isolated duodenal gastrinoma was removed endoscopically with subsequent recovery from the Zollinger-Ellison syndrome. Study of the serum gastrin concentration with provocative tests allowed the Zollinger-Ellison syndrome to be diagnosed and the radicality of duodenal gastrinoma removal to be controlled. Retrograde duodenoscopy conducted after resection of the gastric stump by the Billroth II method localized the source of hypergastrinemia and made possible radical removal of the duodenal gastrinoma, which was confirmed by normalization of the blood serum gastrin concentration. The work includes a brief literature reference on the subject.