Investigation of radiation safety management of nuclear medicine facilities in Japan; contamination of radioactivity in the draining-water system. A Working Group of Japanese Society of Nuclear Medicine for the Guidelines of Nuclear Medicine Therapy

Radiation safety management condition in Japanese nuclear medicine facilities were investigated by the questionnaire method. The first questionnaire was asked in all Japanese 1,401 Nuclear Medicine facilities. Answers from 624 institutes (44.5%) were received and analyzed. The radiation-safety management in nuclear medicine institutes was considered to be very well performed everyday. Opinion for the present legal control of nuclear medicine institutes was that the regulation in Japan was too strict for the clinical use of radionuclides. The current regulation is based on the assumption that 1% of all radioactivity used in nuclear medicine institutes contaminates into the draining-water system. The second questionnaire detailing the contamination of radioactivity in the draining-water system was sent to 128 institutes, and 64 answers were received. Of them, 42 institutes were considered to be enough to evaluate the contamination of radioactivity in the draining-water system. There was no difference between 624 institutes answered to the first questionnaire and 42 institutes, where the radioactivity in the draining-water system was measured, in the distribution of the institute size, draining-water system equipment and the radioactivity measuring method, and these 42 institutes seemed to be representative of Japanese nuclear medicine institutes. Contamination rate of radioactivity into the draining system was calculated by the value of radioactivity in the collecting tank divided by the amount of radionuclides used daily in each institute. The institutes were divided into two categories on the basis of nuclear medicine practice pattern; type A: in-vivo use only and type B: both in-vivo and in-vitro use. The contamination rate in 27 type A institutes did not exceed 0.01%, whereas in 15 type B institutes the contamination rate distributed widely from undetectable to above 1%. These results indicated that the present regulation for the draining-water system, which assumed that 1% of all radioactivity used in nuclear medicine institutes contaminated into draining-water system, should be reconsidered in nuclear medicine facilities where radionuclides are used only in in-vivo studies.     

Dynamic 99Tcm-ECD SPET correlates well with 201Tl indices in brain tumours

The dynamic 99Tcm-ethyl cysteinate dimer (99Tcm-ECD) single photon emission tomographic (SPET) characteristics of brain tumours were investigated and compared with 201Tl-chloride SPET indices. Thirty-five patients with histologically confirmed benign and malignant tumours were evaluated using dynamic and standard 99Tcm-ECD. Twenty-eight patients were also examined using standard 201Tl SPET. The following 201Tl indices were calculated: early uptake ratio, delayed uptake ratio, washout rate and retention index. The relationship between uptake of 99Tcm-ECD on dynamic SPET and 201Tl indices was analysed. Nine patients showed positive uptake on dynamic 99Tcm-ECD SPET, all of whom had benign tumours, including five meningothelial meningiomas, three pituitary adenomas of the chromophobe type and one chemodectoma without malignancy. The mean early uptake ratio of the tumours with positive uptake was significantly higher than that of the tumours with negative uptake (17.1 +/- 5.5 vs 9.0 +/- 5.7, P = 0.004). The mean washout rate of the tumours with positive uptake was significantly higher than that of the tumours with negative uptake (61.0 +/- 27.7 vs 0.35 +/- 30.9, P = 0.0004). The mean retention index of the tumours with positive uptake was significantly lower than that of the tumours with negative uptake (0.27 +/- 0.12 vs 0.88 +/- 0.48, P = 0.000006). Only benign tumours showed positive uptake on dynamic 99Tcm-ECD SPET. The 201Tl indices correlated well with the uptake of 99Tcm-ECD on dynamic SPET. The results suggest that dynamic 99Tcm-ECD SPET can identify the benign character of tumours of the brain.     

Evaluation of the accuracy of preoperative staging in thoracic esophageal cancer

Background. Exact clinical staging before treatment of esophageal cancer has become increasingly important in the evaluation and comparison of the results of different treatment modalities, including surgery, chemotherapy, and radiotherapy.

Methods. The accuracy of preoperative tumor staging by using an esophagography, esophagoscopy, percutaneous and endoscopic ultrasonography, and computed tomography was assessed in 224 patients with resectable esophageal cancer. The results of tumor staging by these tests were compared prospectively with the pathologic stage of the esophagectomy specimens with respect to the T and N categories defined by the International Union Against Cancer TNM classification.

Results. For the T category, the overall accuracy was 80%. For the N category, overall accuracy was 72%, with a sensitivity of 78%, a specificity of 60%, and a positive predictive value of 78%. Overall, the accuracy of stage grouping was 56%.

Conclusions. Either the T or N categories can be predicted reliably by clinical staging techniques. However, the preoperative stage grouping might not be valid in resectable, localized esophageal cancer.     

Prototype of a new pediatric emergency scale tape: PES tape

Drug dosage and appropriate size of medical equipment for emergency pediatric patients are determined by age, body weight and/or height. In an emergency situation, however, such information about the patients is not always clear. Body height is easily measured when the patient lies down supine. Furthermore, child's height could be a better parameter than age to predict appropriate endotracheal tube (ETT) size and body weight. We propose a new pediatric emergency scale tape (PES Tape). PES Tape is graduated in centimeters to measure body height in supine position. Height-based body weight, drug dosage, energy dosage for defibrillation, appropriate size of ETT and lip-tip distance (LTD) are printed on the tape. We studied the reliability of this tape in pediatric anesthesia. Body weight estimated from the tape was accurate, and predicted size of ETT and LTD was appropriate. PES Tape is a reliable tool in pediatric emergency.     

Characterizations of mouse hepatic microsomal monooxygenase catalyzing 11beta-hydroxylation of osaterone acetate.

Osaterone acetate (17alpha-acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,20-dione, OA) is a new steroidal antiandrogen. There is a marked species difference in the metabolism of OA in that 11beta-hydroxylated metabolites are found in the plasma, feces, and urine of mice after oral administration of OA, but there is very little metabolism in rats and humans. OA reduces the adrenal gland weight in mice, but not in rats, and this effect in mice might be explained by the species difference in 11beta-hydroxylation activity. The objectives of this study were to elucidate the enzyme(s) involved in this particular oxidation and to explain the species difference observed. Mouse hepatic microsomes oxidize OA to 11beta-OH OA, and this oxidation requires NADPH as a cofactor. The use of various competitive and allosteric inhibitors of cytochrome P450 and flavin-containing monooxygenase (i.e. CO, N-octylamine, and methimazole) showed that the oxidation of OA was catalyzed by cytochrome P450. In microsomes from mice pretreated with phenobarbital (a CYP2B-selective inducer), 3-methylcholanthrene (a CYP1A-selective inducer), pregnenolone-16alpha-carbonitrile (a CYP3A-selective inducer), and EtOH (a CYP2E-selective inducer), an increase in the rates of oxidation was seen only in microsomes from EtOH-treated animals. However, metyrapone, a selective inhibitor for enzymes of the cytochrome P45011B and P4502B family, inhibited mouse hepatic microsomal 11beta-hydroxylation by < 30%. The results obtained showed that the production of 11beta-OH OA may be catalyzed by a novel cytochrome P450 in mouse liver.     

Separation and analysis of saccharides--on mainly oligosaccharides

Characteristics of three kinds of columns used for the separation and analyses of saccharides by HPLC, and of a pulsed amperometric detector (PAD) as a high sensitive detector for the microanalysis of saccharides were described. The following several examples of studies on the separation and analyses of saccharides were illustrated: (1) separation of maltosaccharides on an amino column, (2) isolation of each maltooligomer of DP6-17 on an ODS column, (3) retention behavior of alpha-cyclodextrin (alpha CD) and branched alpha CDs on an ODS column, (4) separation of three positional isomers of dimaltosyl-beta CD on an ODS column and a graphitized carbon (GC) column, (5) separation of diastereoisomers of glucosyl-inositol on a GC column, (6) chromatographic behavior of nine glucobioses on a GC column, (7) estimation of the distributions of chain length of amylopectins with the pulsed amperometric detection, (8) microanalysis of beta CD and glucosyl-beta CD in biological matrices by HPLC with PAD. In addition, methods for the structural analyses of branched CDs by FAB-MS, 13C-NMR and enzymatic degradation were expressed.     

Kinetics of d-tubocurarine disposition and pharmacologic response in rats

After bolus intravenous dosing of d-tubocurarine (d-TC) to rats, the twitch heights of the tibialis anterior muscle indirectly stimulated were followed, and its decrease was defined as pharmacologic response of d-TC. The relation between dose and response intensity was found to be well described with Hill's equation. According to a theory proposed by Smolen, Hill's equation was also applicable to the biophase d-TC concentration-response relation; the time courses of the relative biophase d-TC concentration indicated linear kinetics with dose levels 0.15 mg/kg and the occurrence of dose-dependent disposition with 0.30 mg/kg. After bolus i.v. dosing of³H-d-TC, plasma d-TC concentration obeyed a dose-independent two compartment model with doses 0.15mg/kg, but not with 0.30 mg/kg. This finding matched the above estimated with pharmacologic data. The active metabolite was not found in plasma and urine. The extent of d-TC plasma protein binding was independent of the wide range of plasma levels and its mean (±SD) value was 30.5 (±3.8). Plasma d-TC levels and pharmacologie response intensity were well correlated by Hill's equation and a three compartment model (the general two and the biophase compartments) in the dose range 0.15 mg/kg.This work was presented at the First Japanese-American Symposium on Pharmacokinetics and Biopharmaceutics, Tokyo, July 1981, which was held in memory of Dr. Sidney Riegelman.     

Reciprocal and non-reciprocal action of the vagal and sympathetic nerves innervating the heart

Simultaneous recordings were made from vagal and sympathetic fibers innervating the heart in dogs anesthetized with chloralose. Reciprocal relationship between the two autonomic nerves was clearly seen in the baroreceptor reflex. Stimulation of chemoreceptors, however, evoked non-reciprocal responses of the two nerves; at the onset of the chemoreceptor reflex cardiac vagal and sympathetic discharges both increased, then, as baroreceptors became excited due to a pressor response, sympathetic nerve activity suddenly decreased while vagal discharges remained high, indicating the appearance of the reciprocal action typifying the baroreceptor reflex. Decrease in ventilatory volume and a slight increase in end-expired CO2 level augmented greatly both vagal and sympathetic discharges. As the phrenic-locked activity of the two nerves (i.e. the activity in vagus nerve occurs only in the absence of phrenic bursts while sympathetic discharges increase with phrenic bursts) increased, the alternate discharges between the two nerves became more conspicuous and the heart rate fluctuated with the respiratory (phrenic) rhythm. Thus, strong reciprocity between vagus and sympathetic can result in an oscillatory heart rate. When ventilatory volume was increased, both nerve activities decreased below control level. Mild hypoxia had similar effects to hypercapnia though changes in nerve activity were greater. When coactivation of vagal and sympathetic nerve was produced in reflex action, changes in vagal discharges occurred earlier and faster than in the sympathetic fibers. The magnitude of change in vagus activity was also far greater. The elimination of afferents in the vagi, the aortic and sinus nerves reduced cardiac vagal activity greatly. However, discharges were still present and occurred between phrenic bursts, indicating that the vagal "tone" is maintained centrally as well as peripherally by input from receptors in the cardiovascular system. The physiological significance of reciprocal and non-reciprocal control of vagal and sympathetic nerves innervating the heart was discussed.     

Influence of the radioactive strontium (89Sr) using for nuclear medical radiation therapy upon radioactive draining-water system

PURPOSE: Strontium-89 chloride (89Sr) is a new radiopharmaceutical that provides effective pain relief for metastatic bone lesions, and is expected to be available soon in the palliative management for metastatic bone pain in Japan. Because of relatively long physical half life (50.5 days), 89Sr may affect to the radioactive draining-water system by exceeding the limits of activity concentration for radioactive drain. In this article, the influence of 89Sr use on the radioactive drainage system was simulated. METHODS: The standard tank capacity of drainage and draining frequency was determined from the results of questionnaire carried out for the nationwide medical and research institutes where radioisotope treatment are performed. On the assumption that 89Sr of 148 MBq for one therapy was used twice a week and several common radionuclides were used as the same activity as used at Chiba Cancer Center, the influence of 89Sr was estimated. The calculation was performed using the activity contamination ration into the draining-water system of each radionuclide of 0.01, which was legally determined. RESULTS: The simulation revealed that the sum of the contamination ratios of individual radionuclides exceeded a legal value of 1.0 in standard drainage with the capacity of 5 m3 and 10 m3 and draining frequency of 7 times per year. The actual contamination ratios of common radiopharmaceuticals measured at Chiba Cancer Center ranged from 1/100 to 1/1000 of the legal values. CONCLUSION: It is necessary that the legal value of activity contamination ratios into the draining-water system should be reassessed before starting 89Sr therapy.     

Radiographic Diagnosis of Early Colorectal Cancer, with Special Reference to the Superficial Type of Invasive Carcinoma

The possibility of radiographically diagnosing carcinoma with submucosal involvement (invasive carcinoma) is discussed based on 119 invasive carcinomas of the large bowel that had been treated surgically and colonoscopically over a period of 9 years (1989—1997) at the Cancer Institute Hospital in Tokyo. Of these lesions, 38 were superficial-type invasive carcinoma, accounting for 31.9% (38/119) of all invasive colorectal carcinomas, including 36 lesions (94.7%, 36/38) of types IIa and IIa+IIc and 2 lesions (5.3%, 2/38) of type IIc+IIa. No pure type IIc was seen. The radiographic images obtained were correlated with macroscopic findings and analyzed in terms of visualization of the lesion's contour, central depression, converging folds, and basal indentation. A definitive diagnosis of superficial invasive carcinoma can be made radiographically if a lesion measures 10 mm and reveals moderate to severe basal indentation in a complete or nearly complete profile radiographic image. Attention should be paid to the presence of superficial-type advanced carcinomas measuring 10 mm or less, which is not infrequently experienced in Japan. Polypoid invasive carcinoma can be definitively diagnosed in the same way with much more certainty than can the superficial type because few polypoid advanced carcinomas are less than 20 mm. The size and the radiographic sign of the basal indentation are the most important indicators for the diagnosis of invasive carcinoma. E-pub: 27 July 2000