Quarter Dose Research Articles

AN ANALYSIS OF VARIABLES INFLUENCING THE NUMBER OF RADIATION OVEREXPOSURE EVENTS IN TEXAS FROM 1970 TO 2000

Sources of radiation are used in a variety of modern work settings, including industrial, medical, research, and agricultural applications. Although regulatory controls exist to limit radiation exposures in these different settings, instances of radiation doses in excess of acceptable limits (referred to as overexposures) do occur. A unique study examined overexposure events in Texas over a 45-y period from 1956 to 2001. The primary purpose of the study was to characterize the factors associated with overexposure events. As part of this characterization, an interesting trend in the number of overexposures by year was observed, but not completely explained. The data revealed a dramatic increase in the number of overexposure events, followed by three apparent phases of decline. These declines are of particular interest because, while the increase and subsequent decrease in overexposures occurred, the number of permits to possess radiation sources in Texas generally increased over the same time period. This study focused on the identification of the factors that led to the trends in overexposure events. Data describing the reported overexposure events in Texas from 1970 to 2000 were obtained from the Texas Department of Health Bureau of Radiation Control (TDH BRC) and entered into a computerized database. With the assistance of senior members of the TDH BRC, the three primary factors influencing the number of overexposures were identified. These included domestic oil and gas exploration and production from 1970 to 2000, wherein sources of radiation are employed in various operations; the establishment of a training and certification requirement for industrial radiographers during the period of 1986 to 1988; and modification of the applicable regulations between 1992 and 1994. The generally accepted indicator of oil and gas exploration and production activity, known as "rig count," is the measure of the number of active oil and gas exploration and production platforms at any given time. Rig count is a parameter of particular interest in Texas because the state's economy is significantly tied to the market value of this important natural resource. The rig count parameter was shown to have a strong correlation with overexposure events (Pearson correlation coefficient of 0.82, p < 0.0001). Interestingly, the sources causing the overexposures indicate that the events stem primarily not from the oil and gas exploration activity itself, but rather from support activities in the form of industrial radiographic procedures. The number of overexposure events was also determined to be influenced by the imposition of the training requirement for radiographers and the modification of the applicable regulations (e.g., the elimination of the quarterly dose limit). The relative magnitude of these influences, however, was far overshadowed by the identified predominant predictor of rig count. The determination of rig count as the significant influencing factor in overexposure events is useful in possibly recognizing the potential for future occurrences of the same nature. This assessment also serves to highlight an apparent significant public health success story, as the number of overexposures per radioactive material licensee is shown to have declined significantly over the 30-y period of study. The factors contributing to this phenomenon are described to serve as a model for use in other settings.

Long-term environment monitoring based on MTS-N (LiF:Mg, Ti) and MCP-N (LiF:Mg, Cu, P) thermoluminescent detectors

An environmental radiation monitoring system using standard MTS-N (LiF:Mg, Ti) and high-sensitive thermoluminescent LiF:Mg,Cu,P (MCP-N) detectors was applied to control the radiation exposure over the area of the Institute of Nuclear Physics (INP) in Kraków. First environmental measurements using MTS-N detectors began in 1970 at five locations and were continued during the Chernobyl accident at six sites. In March 1987 high-sensitive MCP-N detectors read out in a manual TL reader were first introduced into service at the INP. Since 1992 about 60 locations over an area of the INP were selected for quarterly dose rate measurements, using an automatic TLD system based on MTS-N detectors placed in cards. In 2002 MTS-N detectors were replaced by high-sensitive MCP-N pellets.The dose rate in long-term measurements changed over the last 30 years. The average gamma dose rate over the area of INP in the years 1975–1978 was 63nGy−1. After the Chernobyl accident the gamma dose rate increased to 880nGyh−1. In December 1986 the dose rate at the location place decreased to 103nGyh−1. At present, the average dose rate has returned to the pre-Chernobyl level of about 68nGyh−1. Construction and beam tests of a new isochronous cyclotron at the INP resulted in highly enhanced environmental dose rates at several monitored INP sites. In this work results of almost 11 years of environmental indoor and outdoor measurements with thermoluminescent detectors are summarised.

Cost‐benefits of reduced aphicide usage on dwarf hops susceptible and partially resistant to damson‐hop aphid

SummarySoil‐applied imidacloprid at full (125 g a.i. ha−1) and half approved doses gave levels of control of damson‐hop aphid, (Phorodon humuli), similar to that provided by foliar spray(s) of tebufenpyrad on the aphid‐susceptible dwarf hop cvs First Gold and Herald. On those cultivars, aphid control was unreliable on plots treated with quarter dose imidacloprid and was generally no better than on untreated plants. Aphids were virtually eliminated from the leaves by the end of July each year in all treatments consistent with the action of natural enemies. Aphid contamination of cones reflected the numbers on foliage at flowering time, but varied widely between years. Yields and percentage α‐acids content of dried hops were unaffected by the numbers of aphids on leaves early in the season and in cones at harvest, but aphid contamination reduced the economic values of crops by as much as 80%. Few P. humuli colonised the partially aphid‐resistant breeding line 23/90/08 before their numbers were regulated and consistent with natural enemy activity. Yields, percentage α‐acids content, and commercial value of harvested cones were similar in all treatments on 23/90/08 whether or not plants were treated with aphicides. The commercial risks posed by P. humuli preclude substantial reductions in aphicide usage on aphid‐susceptible dwarf hop cultivars, but future cultivars expressing a similar level of partial resistance to aphids as 23/90/08 should not need treatment with aphicides.

Field evaluations of the VD max approach for substantiation of a 25 kGy sterilization dose and its application to other preselected doses

The International and European standards for radiation sterilization require evidence of the effectiveness of a minimum sterilization dose of 25 kGy but do not provide detailed guidance on how this evidence can be generated. An approach, designated VD max, has recently been described and computer evaluated to provide safe and unambiguous substantiation of a 25 kGy sterilization dose. The approach has been further developed into a practical method, which has been subjected to field evaluations at three manufacturing facilities which produce different types of medical devices. The three facilities each used a different overall evaluation strategy: Facility A used VD max for quarterly dose audits; Facility B compared VD max and Method 1 in side-by-side parallel experiments; and Facility C, a new facility at start-up, used VD max for initial substantiation of 25 kGy and subsequent quarterly dose audits. A common element at all three facilities was the use of 10 product units for irradiation in the verification dose experiment. The field evaluations of the VD max method were successful at all three facilities; they included many different types of medical devices/product families with a wide range of average bioburden and sample item portion values used in the verification dose experiments. Overall, around 500 verification dose experiments were performed and no failures were observed. In the side-by-side parallel experiments, the outcomes of the VD max experiments were consistent with the outcomes observed with Method 1. The VD max approach has been extended to sterilization doses >25 and <25 kGy; verification doses have been derived for sterilization doses of 15, 20, 30, and 35 kGy. Widespread application of the VD max method for doses other than 25 kGy must await controlled field evaluations and the development of appropriate specifications/standards.

Frequency of Positive Biopsies after Visual Disappearance of Superficial Bladder Cancer Marker Lesions

Introduction and Objectives: In phase II trials in superficial bladder cancer, marker lesions have been used to test the ablative activity of intravesical chemo– or immunotherapy. These studies provide important knowledge about drug activity and toxicity without exposing hundreds of patients in phase III trials to drugs which ultimately may not be successful in preventing tumour recurrence or progression. After treatment a deep biopsy was necessary at the site of the marker lesion even in the absence of any visual tumour. The question is if this biopsy, in the absence of any visual tumour, should be done. Material and Methods: The ablative effect of MMC, epirubicin, and quarter dose BCG instillations was evaluated in three different studies on a papillary marker lesion. Patients with multiple, primary or recurrent superficial bladder tumours were included. All visible Ta–T1 lesions were resected except for one marker lesion not exceeding 1 cm. TIS was excluded. In the last study, patients with T1 G3 tumours or multiple tumours >10 were also excluded. If the marker lesion disappeared completely, a deep biopsy was performed at the scar in order to prove histological disappearance of the tumour. Results: 185 patients were evaluated. No visual tumours were seen in 110 patients and a TUR was performed in 101 of them. It revealed only 3 Ta lesions. In the 9 others no biopsy was performed but follow–up cystoscopy revealed no lesions. Conclusions: In the absence of any visual tumors, TUR and deep biopsy at the site of the scar of the marker lesion only rarely revealed (3 out of 110) the histological presence of a tumour. Therefore, this biopsy can be omitted in new marker lesion protocols in patient with Ta–T1, G1 G2 papillary superficial bladder tumours at intermediate risk for recurrence and low risk for progression.

THE ABLATIVE EFFECT OF QUARTER DOSE BACILLUS CALMETTE-GUERIN ON A PAPILLARY MARKER LESION OF THE BLADDER

Low dose bacillus Calmette-Guerin (BCG) for stage TaT1 transitional cell carcinoma of the bladder has been given in various studies with the aim of decreasing side effects while maintaining the same efficacy as full dose bacillus Calmette-Guerin. However, its application in clinical practice remains controversial. We examined the ablative activity and incidence of side effects of intravesical quarter dose BCG given for a papillary marker lesion of the bladder. Included in our study were 44 patients with primary or recurrent, multiple but no more than 10 lesions of stage pTaT1, grades 1 to 2 transitional cell carcinoma of the bladder. Intravesical treatment begun 14 days after the complete transurethral resection of all visible tumors except 1 marker lesion no larger than 1 cm. consisted of instillations of 30 mg. Connaught strain BCG diluted in 50 ml. saline once weekly for 6 consecutive weeks. Two weeks after the last instillation any residual tumor was completely resected. In cases of complete disappearance of the marker lesion deep biopsy of the tumor area was done. Urine cytology was also performed. There was a complete response in 27 of the 44 patients (61%), no response in 12 (27%) and progression to carcinoma in situ in 1 (2%), while the response was not evaluable in 4. Local side effects included dysuria in 54% of cases and macroscopic hematuria in 39%. Neither BCG induced infection nor BCG sepsis was observed. Quarter dose BCG has a clear ablative effect on superficial bladder cancer with a 61% response rate. Phase III trials are now required to compare its efficacy and toxicity to those of full dose BCG.

Effects of low dose mixtures of four N-nitroso compounds on hepatic foci development in the rat.

Potential synergism between four N-nitroso compounds (nitrosomorpholine, nitrosodimethylamine, nitrosodiethanolamine, nitroso-oxazolidine) in rat liver carcinogenesis was examined in the medium-term bioassay. Male F344 rats were initially given diethylnitrosamine (DEN, 200 mg/kg, ip) and beginning 2 weeks later received test chemicals for 6 weeks individually at a full or 1/4 dose of that proven to be carcinogenic individually or in combination. All animals were subjected to partial hepatectomy at week 3 and killed at week 8. Induction of immunohistochemically-demonstrated glutathione S-transferase placental form (GST-P) positive foci was evaluated. The numbers and size of GST-P positive foci were significantly higher than the control levels by the treatment with each nitrosamine at full (1/1) and one quarter doses (1/4), excepting nitrosodiethanolamine and by combination of the four chemicals at 1/4 and 1/16. Because the dose-response curves were considered non-linear for most nitrosamines, synergistic effects were not apparent for the 1/4 mixture. Interestingly, however, the values for rats treated with these four chemicals in combination at the 1/4 dose level were almost the same as the average of four individual treatments at the full dose, and those for the 1/16 dose mixture were almost the same as the average of 1/4 individual treatment groups. These results indicate that these nitrosamines worked additively, rather than synergistically, in rat liver carcinogenesis.

Stimulation of plant growth and aphid populations by a formulation ingredient of ‘Cymbush’ (cypermethrin)

AbstractSimilar increases in the height and aerial fresh weight of cowpeas compared with control plants were obtained when plants were sprayed with either 50 ppm a.i. (active ingredient) of the pyrethroid insecticide ‘Cymbush’® containing cypermethrin, or, the equivalent dilution of a blank formulation without the a.i. With broad beans, similar growth stimulation was obtained with the blank at the same or half dose, but not at a quarter dose. Testing the four formulation components separately showed that only the non-ionic emulsifier caused stimulation. A comparison of the stimulation of plant growth by the blank and the non-ionic emulsifier showed that plant height, shoot fresh weight, leaf fresh weight, leaf dry weight and leaf area were each equally increased by both treatments. The non-ionic emulsifier thus accounted for the entire stimulation caused by blank solution. Populations of Aphis fabae Scopoli (Homoptera: Aphididae) were twice as high on broad bean plants sprayed with the non-ionic emulsifier as on the controls. ‘Cymbush’ (the complete formulation) sprayed at 25 ppm a.i. was shown to increase the intrinsic rate of natural increase of the aphid through a 22% increase in fecundity; aphid development time was not affected. The results do, however, suggest that residual effects of cypermethrin may have partly counteracted the stimulatory effects of the non-ionic emulsifier. Nevertheless, it is possible that outbreaks of aphids and mites following pyrethroid application, and often assumed without evidence to have been due to natural enemy mortality, may at least in part reflect the plant stimulation caused by the non-ionic emulsifier in the formulation.

Comparative trial of administration of half (0.05 mg) and quarter (0.025 mg) dose of intradermal Pasteur BCG on 291 infants from birth to 1 year in French Guyana

The study concerns 291 newborns and infants aged 0 to 1 year placed randomly in two groups which respectively received 0.025 and 0.05 mg Pasteur BCG by intradermal injection, between 1 December 1988 and 28 February 1989. This random test aimed to determine if the administration of one quarter dose (0.025 mg) of intradermal BCG conferred immunity comparable to that of one half (0.05 mg) while diminishing the risk of complications, in particular suppurative adenopathy, in infants of ages 0–1 year. Statistical analysis of the results showed that the 0.025 mg dose of intradermal BCG entails an immunoresponse as satisfactory as that entailed by the 0.05 mg dose, while the rate of suppurative adenitis is significantly higher in the group that received the 0.05 mg dose. It is therefore well justified to recommend a dose of 0.025 mg of intradermal Pasteur BCG for infants aged 1 year and less.

FIRST-YEAR CHANGES IN BLOOD LEAD AND ZINC PROTOPORPHYRIN LEVELS WITHIN TWO GROUPS OF OCCUPATIONAL LEAD WORKERS

Quarterly changes in blood lead (PbB) and zinc protoporphyrin (ZPP) levels experienced by 30 male lead-acid storage battery workers and 24 auto assembly workers during their initial year of occupational lead exposure are described. The greatest absolute and percentage increases above baseline PbB levels occurred during the first 3 months of continuous exposure when battery and assembly workers' average PbB levels increased by 99% and 134%, respectively. Peak average PbB levels were reached during the second quarter of exposure for battery workers (27.3 micrograms/dL) and during the third quarter for assembly workers (34.3 micrograms/dL). Mean ZPP levels increased steadily through the first 3 quarters of exposure for both groups of workers before declining slightly during the final 3 months. Third-quarter average ZPP levels were 46.6 micrograms/dL for battery workers and 59.4 micrograms/dL for assembly workers. In general, for the assembly workers, the slopes of quarterly dose (PbB)-effect (loge ZPP) regressions increased with increasing exposure duration (up to 0.044 by the third quarter of exposure) and were significant (p less than 0.0001). Similar calculations for the battery workers were not statistically significant (p greater than 0.05) and showed no exposure-related trends. Probit-based dose (PbB)-response (ZPP level greater than two standard deviations above the baseline ZPP) analyses of the assembly worker data resulted in a 30.0 micrograms/dL ED50 estimate (PbB concentration at which 50% of a similarly exposed population would be expected to develop an "elevated" ZPP level).(ABSTRACT TRUNCATED AT 250 WORDS)

Standard and reduced doses of sulfadoxine-pyrimethamine for treatment of Plasmodium falciparum in Tanzania, with determination of drug concentrations and susceptibility in vitro

88 asymptomatic Tanzanian schoolchildren with Plasmodium falciparum parasitaemia were given all, half or quarter of the recommended standard therapeutic dose of sulfadoxine-pyrimethamine (Fansidar ®). All children cleared the parasites by day 3 and all remained negative during 28–42 days of follow-up. All 32 successful in vitro micro-tests showed full sensitivity. High performance liquid Chromatographic methods were applied for drug determinations. Using 100 μ1 capillary blood dried on filter paper for sulfadoxine determination the interindividual variation during follow-up of the standard dose group was 2–4 fold and the median half life was 8·9 d. Sulfadoxine concentrations in the half and quarter dose groups were roughly proportional to those in the standard dose group. The median whole blood to plasma concentration ratio for sulfadoxine was 0·72 and the correlation coefficient 0·95. There was only a weak correlation ( r = 0·46) between plasma concentrations of sulfadoxine and pyrimethamine. The uniform efficacy of sulfadoxine-pyrimethamine in vivo, even when reduced doses were used, makes this combination a good alternative for treatment of P. falciparum in Tanzania.

Epidemiology and control of ascariasis in Korea

In view of the epidemiology and control strategy, ascariasis was reviewed with special reference to the data obtained for the past years in Korea. The range of length and prepatent period of A. lumbricoides to become fertile were 12.5-13.5 cm and 1.8-2.1 months for females, and 10.5-11.5 cm and 2.1-2.5 months for males, respectively. In the female worm burden 1 per case, the egglaying capacity steadily increased from 12.6 cm of their length up to 25.0 cm and then decreased significantly after their growth to 27.5 cm. Analysed the egg discharging pattern, it was turned out that the cases with six or more worms have no probability to be false negative or unfertilized ova passer, and 52% of all false negatives were found infected only with male(s). The sex ratio was in the range of 0.74-0.82 (male/female). Basic reproductive rate was calculated in the range of 1.16-2.11 in rural areas, but it was approaching nearly to the 'break point' in some areas. It was observed that the 'U-rate' was increased from 19.4% (1973) to 61.1% (1989) for the past seventeen years. According to the survey in 6 rural areas, the average worm burden was 2.2 per population and 4.5 per infected. The frequency distribution pattern of A. lumbricoides per person in a rural community was well fitted to the negative binomial distribution. Seasonal fluctuation was shown in two, smaller and larger, peaks. The annual prevalence in student group was initially 55.4% in 1969, but decreased to 0.3% in 1989, and it is evident that the decrease has been greatly owing to the national control project. It was proved that the efficacy of a quarter dose of pyrantel pamoate used in long term control programme was almost equal to that of conventional dose (10 mg/kg). The comparatie efficacy of various interval mass chemotherapy schemes was evaluated through 2 year observations, and it was confirmed that at least biannual mass chemotherapy is necessitated to expect gradual lowering of reinfection. In the case of blanket treatments with 2-month interval in a village, all of inhabitants have been free from reinfection for the period of 28 months after the initial treatment. It was fully recognized that without specific legislation and organization supported by the government, the national mass control programme has almost no chance of success, especially in developing countries.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect Of Two-Month Interval Mass Chemotherapy On The Reinfection Of Ascaris Lumbricoides In Korea.

Atrial to control reinfection cycle of Ascaris lumbricoides was made in a rural village in Korea by blocking the process of new egg production. Chemotherapy with pyrantel pamoate was repeated bimonthly in three hamlet groups, each consisted of 105~149 inhabitants of whole age group. In one hamlet (2.5 mg/kg dose) blanket mass treatment was repeated for 18 times from June 1977 to May 1980. In other two, 5.0 mg and 10.0 mg/kg dose groups, treatment was undertaken for 10 times from June 1977 until December 1987 and later reinfection patten was observed. Follow-up examination was made by whole-day stool collection for 2 days from each case after every treatment. The samples were examined both for eggs and worms, adult and immature young, of A. lumbricoides. The results obtained are summarized as follows: 1. The pre-treatment egg positive rate in Group A, B and C was 48.1, 45.3 an 37.8% respectively. 2. The lowest dose of pyrantel pamoate, 2.5 mg/kg was equally effective as higher doses in case of repeated use for reinfection control. 3. Among 4,311 pyrantel treatments, only 8 cases complained of side effects such as abdominal pain and diarrhea. 4. When the blanket mass chemotherapy was continued 18 times in Group A, all of the examined inhabitants were free from reinfection and egg production from 28th month (the 15th treatment) until the end of study period, for 8 months. 5. When the mass chemotherapy was stopped after 10 times, the egg positive rate returned gradually up to half of pre-treatment level within one year. 6. From the analysis of total 124 positive cases during the course of follow-up, it was revealed that the mass chemotherapy with 2-month interval was successful for the suppression of fertilized egg production. However, social factors such as infected immigrants or absentees were inevitably encountered and involved in the fertilized egg production. Summarizing the results, at least 28-30 months were needed to eradicate A. lumbricoides in the subjected area of Korea, by repeated blanket mass treatment bimonthly with a quarter dose of pyrantel pamoate. Furthermore, to lessen the social factors as a source of later reinfetion, the project area of control programme should be extended as wide as possible.

Ticrynafen: kinetics, protein binding, and effects on serum and urinary uric acid.

The kinetics and acute effects of ticrynafen, a new diuretic and uricosuric, have been studied in 4 normal subjects. In 3 of the 4 subjects given a 250‐mg tablet, peak plasma ticrynafen concentrations of 15 to 35 µg/ml were achieved at 1 to 2 hr; in the fourth subject a peak concentration of 10 µg/ml was attained at 6 hr. Elimination half‐life was 2.0 to 3.3 hr. Bioavailability covered a 2.5‐fold range (61.7–154.6 µg · hr · ml−1). Administration of the same dose as quarter doses at 2 hr intervals produced a progressive rise in plasma ticrynafen concentration to 5.5 to 12.9 µg/ml at 8 hr and thereafter a decline at a similar rate to that seen with the single dose. The hypouricemic effect was similar for the single‐ and divided‐dose treatments: uric acid concentration began to fall within 1 hr, reached a minimum of 53% to 77% of the pre‐drug value at 7 to 10 hr, and had returned to approximately pre‐drug values at 24 hr. Urinary uric acid excretion was significantly increased for up to 12 hr with both treatments. The diuretic effect of the single dose lasted 4 to 8 hr, while that of the divided dose lasted 8 to 12 hr.

Predicted and Measured Exposures from 41Ar Released to the Atmosphere by a Heavy Water Research Reactor

The gamma dose around the Taiwan Research Reactor (TRR) due to an accumulated cloud of 41 Ar was estimated by both theoretical and experimental methods. In this study, four special considerations were included in the calculations in order to produce accurate quarterly dose estimates. First, a precise calculation was carried out to obtain upwind, downwind and crosswind dose distributions under different weather categories. Second, the Ar-41 dose distributions were weighted not only by the joint frequency of occurrence of wind speed, wind direction and stability but also by the reactor operating power level. Third, in addition to the downwind dose distributions, the crosswind dose distributions were taken into account to estimate the dose received by the receptor. Fourth, for a receptor located within 500 m of the reactor stack, the upwind exposure was taken into account. Five groups of accumulated dose data were obtained for five consecutive quarters at each of the dosimetry stations. The stations ranged in location from about 100 to 1200 m from the reactor stack. Except for those data within 100 m of the stack, the calculated values are within ±26% of the measured values.