Rapid rejoining of DNA strand breaks in resting human lymphocytes after irradiation by low doses of 60Co gamma rays or 14.6-MeV neutrons.

The production and repair of DNA strand breaks was studied in human lymphocytes by means of a sensitive fluorometric technique. Lymphocytes were isolated by conventional methods and air-equilibrated suspensions were irradiated by low doses (less than or equal to 2 Gy) of either 60Co gamma rays or 14.6-MeV neutrons at 0 degree C. The apparent yield of initial strand breaks induced by neutrons was only 36% of that induced by gamma rays, in agreement with the observations of other workers. Resting lymphocytes were found to be proficient in their ability to rejoin gamma-induced strand breaks at 37 degrees C; rejoining followed biphasic kinetics, with 70% of the breaks disappearing with a half-life of about 3 min. Although the initial number of breaks induced by neutron irradiation was low, after 20 min of incubation the residual number of breaks was very similar for the two forms of radiation.

Laminaria as an adjunct in induction of labor.

The safety and efficacy of laminaria tents as an adjunct to labor induction near term were examined in a prospective, controlled, and randomized study involving insertion of laminaria into the cervical canal the evening prior to planned induction. Six of 35 subjects in whom laminaria were used entered labor spontaneously and delivered overnight, compared with 1 of 39 controls. Of the remainder, the Bishop score increased an average of 3.7 points, a highly significant change, in the laminaria-treated group compared with no change in the controls. Labor, induced primarily by amniotomy with intravenous oxytocin then given to patients in whom regular contractions did not begin within 8 hours, was shorter with laminaria use than in controls, though the amniotomy-to-delivery interval did not differ significantly. However, comparison of the subgroup with cervices relatively unfavorable for induction, indicated by an initial Bishop score of 5 or less, showed both length of labor and amniotomy-to-delivery interval to be significantly shorter (each by an average of 3 hours) in the laminaria-treated group compared with controls. Complications, including febrile morbidity, did not differ. We conclude that laminaria tents are both effective and safe as an adjunct to labor induction, acting by accelerating the preparatory changes in the cervix which normally occur in late pregnancy.

Calculation of beta-ray dose distributions from ophthalmic applicators and comparison with measurements in a model eye.

Dose distributions throughout the eye, from three types of beta-ray ophthalmic applicators, were calculated using the EGS4, ACCEPT 3.0, and other Monte Carlo codes. The applicators were those for which doses were measured in a recent international intercomparison [Med. Phys. 28, 1373 (2001)], planar applicators of 106Ru-106Rh and 90Sr-90Y and a concave 106Ru-106Rh applicator. The main purpose was to compare the results of the various codes with average experimental values. For the planar applicators, calculated and measured doses on the source axis agreed within the experimental errors (<10%) to a depth of 7 mm for 106Ru-106Rh and 5 mm for 90Sr-90Y. At greater distances the measured values are larger than those calculated. For the concave 106Ru-106Rh applicator, there was poor agreement among available calculations and only those calculated by ACCEPT 3.0 agreed with measured values. In the past, attempts have been made to derive such dose distributions simply, by integrating the appropriate point-source dose function over the source. Here, we investigated the accuracy of this procedure for encapsulated sources, by comparing such results with values calculated by Monte Carlo. An attempt was made to allow for the effects of the silver source window but no corrections were made for scattering from the source backing. In these circumstances, at 6 mm depth, the difference in the results of the two calculations was 14%-18% for a planar 106Ru-l06Rh applicator and up to 30% for the concave applicator. It becomes worse at greater depths. These errors are probably caused mainly by differences between the spectrum of beta particles transmitted by the silver window and those transmitted by a thickness of water having the same attenuation properties.

Dosimetry of beta-ray ophthalmic applicators: comparison of different measurement methods.

An international intercomparison of the dosimetry of three beta particle emitting ophthalmic applicators was performed, which involved measurements with radiochromic film, thermoluminescence dosimeters (TLDs), alanine pellets, plastic scintillators, extrapolation ionization chambers, a small fixed-volume ionization chambers, a diode detector and a diamond detector. The sources studied were planar applicators of 90Sr-90Y and 106Ru-106Rh, and a concave applicator of 106Ru-106Rh. Comparisons were made of absolute dosimetry determined at 1 mm from the source surface in water or water-equivalent plastic, and relative dosimetry along and perpendicular to the source axes. The results of the intercomparison indicate that the various methods yield consistent absolute dosimetry results at the level of 10%-14% (one standard deviation) depending on the source. For relative dosimetry along the source axis at depths of 5 mm or less, the agreement was 3%-9% (one standard deviation) depending on the source and the depth. Crucial to the proper interpretation of the measurement results is an accurate knowledge of the detector geometry, i.e., sensitive volume and amount of insensitive covering material. From the results of these measurements, functions which describe the relative dose rate along and perpendicular to the source axes are suggested.

Spectra and dosimetry related to neutron irradiations of the human body.

Neutron spectra at various locations in a phantom, irradiated by collimated beams of 14 MeV neutrons and neutrons from 252 Cf and Po-Be sources, were calculated using the Monte Carlo technique. These spectra give an indication of the distortion in source spectra associated with neutron irradiations of the body for therapeutic and diagnostic purposes. The effect of the spectral distortions on the dose response of several activation and damage track detectors was investigated. Of the dosemeters studied, Np has a dose response most nearly independent (+/-10%) of the spectral changes.

Spectral and dosimetric characteristics of a D2O-moderated 252Cf calibration facility.

Calculations have been made for a D2O-moderated 252Cf assembly like that being used for the calibration of neutron dosimeters at the U.S. National Bureau of Standards and being proposed by the International Standards Organization. Leakage spectra at various distances from the assembly are given along with variations in dose-equivalent rate, average neutron energy and 235U/237Np fission ratio. The spectral shape changes rapidly near the spherical assembly and the dose-equivalent rate changes more rapidly than would be expected on the basis of the inverse-square dependence. Calibration of neutron dosimeters should therefore be made at distances greater than 15 cm from the surface. At large distances from the source, the dose equivalent per unit fluence for neutrons above 1 eV is 9.3 X 10(-9) rem cm2. The effects of the structural material, recent revisions to nuclear data files and changes in the spectrum of the source neutrons on the external field were investigated. These changes produce only about a 5% change in the neutron-dose equivalent rate. The structural material introduces negligible anisotropy in the radiation field.

Beta-ray dose distributions from point sources in an infinite water medium.

The ACCEPT Monte Carlo code has been used to calculate radial dose distributions around isotropic point sources of monoenergetic electrons between 0.01 and 10 MeV in an infinite water medium. The results were averaged over beta spectra to derive distributions for 147 beta emitters of which 32 are presented. More extensive tables of distributions will be presented in a report. Distributions for monoenergetic electrons agree with recent ETRAN-code calculations of Berger and Seltzer within 2%, except at very short distances where there are differences up to several percent. Results calculated by the EGS4 code differ by up to a few percent. Distributions for beta emitters are in excellent agreement with both experimental results and ETRAN and EGS4 calculations, except at very short distances.

Calibration of a portable tritium-in-air monitor for various radioactive gases.

A commercially available portable tritium-in-air monitor was calibrated for detecting the concentration of tritium-in-air, 14C-in-air, and various radioactive noble gases. Calibrations were performed both experimentally, using assayed quantities of the calibration gases, and theoretically, by simulating the monitor's response using Monte Carlo code. The experimental and theoretical calibrations agreed within +/- 10% for all gases tested with the exception of 41Ar-in-air where the agreement was approximately 20%. The results show that, although the monitor can be used to measure a wide range of radioactive gases, if more than one gas is present the monitor can not be used to accurately determine the concentration of, and hazard posed by, these gases. It is also shown that the monitor's ability to accurately assess tritium-in-air hazards would be seriously compromised by the presence of other radioactive gases.

DNA strand break and rejoining in cultured human fibroblasts exposed to fast neutrons or gamma rays.

The production and rejoining of DNA single-strand and double-strand breaks have been monitored in monolayer cultures of proliferating human skin fibroblasts by means of sensitive techniques. Cells were irradiated with low doses of either 60Co gamma-rays or 14.6 MeV neutrons at 0 degrees C (0-5 Gy for measurement of single-strand breaks by alkaline elution and 0-50 Gy for double-strand breaks measured by neutral elution). The yield of single-strand breaks induced by neutrons was 30 per cent of that produced by the same dose of gamma-rays; whilst in the induction of double-strand breaks neutrons were 1.6 times as effective as gamma-rays. Upon post-irradiation incubation of cells at 37 degrees C, neutron-induced single-strand and double-strand breaks were rejoined with a similar time-course to gamma-induced breaks. Rejoining followed biphasic kinetics; of the single-strand breaks, 50 per cent disappeared within 2 min after gamma-rays and 6-10 min after neutrons. Fifty per cent of the double-strand breaks disappeared within 10 min, after gamma-rays and neutrons. Cells derived from patients suffering from ataxia-telangiectasia showed the same capacity for repair of single- and double-strand breaks induced by 14.6 MeV neutrons, as cells established from normal donors. The comparison of neutrons and gamma-rays in the induction of DNA breaks did not explain the elevated r.b.e. on high LET radiation. However, a study of the variation in the spectrum of lesions induced by different radiation sources will probably contribute to the clarification of the relative importance of other radio products.

Phase II trial of methotrexate, vinblastine, doxorubicin, and cisplatin in advanced/recurrent carcinoma of the uterine cervix and vagina.

A phase II combination chemotherapy protocol combining methotrexate, vinblastine, doxorubicin, and cisplatin was designed to evaluate tumor response and survival in patients with advanced/recurrent cervix and vaginal cancer. Twenty-nine patients with advanced/recurrent cervix cancer and three patients with advanced vaginal cancer who had not previously received cytotoxic chemotherapy were assigned to chemotherapy treatment at 4-week intervals with methotrexate 30 mg/m2 i.v., Day 1, vinblastine 3 mg/m2 i.v., Days 2, 15, and 22, doxorubicin 30 mg/m2 i.v., Day 2, and cisplatin 70 mg/m2 i.v., Day 2. After a median of 4 cycles (maximum number 2 cycles beyond complete regression; 6 cycles with stable regression); we observed objective regressions in all 3 patients with vaginal cancer and 19 patients (66%, 95% CI = 46.82) with cervix cancer including complete regression in 6 patients (21%, 95% CI = 8.40) and partial regression in 13 patients (45%, 95% CI = 26.64). Median overall survival was 11.5 months (range 1.1-54+). Median survival of responders was 12.8 months (range 3.6-54+). Toxicity included neutropenia, alopecia, nausea, emesis, and stomatitis. Although grade 3 and 4 neutropenia was observed in over half of the patients, there were no treatment-related deaths. In conclusion, MVAC is a highly active outpatient chemotherapy regimen in patients with advanced/recurrent cervix cancer, achieving a high complete and partial response rate with moderate hematologic toxicity. These results need to be confirmed by phase III trial in advanced disease patients and MVAC may be a suitable regimen for investigation in neoadjuvant chemotherapy trials in poor prognosis, previously untreated patients.