Ovarian cyclicity in thyroid-suppressed ewes treated with propylthiouracil immediately before onset of seasonal anestrus.

Two experiments were conducted to determine if propylthiouracil (PTU)-induced thyroid suppression immediately before onset of anestrus would extend the breeding season in mature ewes. In Exp. 1, twice-weekly serum concentrations of progesterone indicated that all ewes were cyclic before initiation of treatment. Beginning on d 0 (January 17), ewes received 0 (n = 4), 20 (n = 5), or 40 (n = 5) mg of PTU x kg(-1) of body weight (BW) x (-1) for 35 d. Blood samples were collected regularly throughout the trial and serum thyroxine and progesterone were quantified. Ewe BW were similar (P > 0.90) among treatments before the experiment began (mean = 78.2 +/- 4.5 kg). Likewise, serum concentrations of thyroxine averaged 86.5 +/- 8.0 ng/mL on d 0. After 11 d of PTU treatment, serum thyroxine was 90.2,75.2, and 44.2 +/- 14.0 ng/mL in ewes receiving 0, 20, and 40 mg of PTU/kg BW, respectively (linear effect, P = 0.04). On d 20, thyroxine values in the three respective groups were 73.0, 51.1, and 16.1 +/- 12.9 ng/mL (linear effect, P < 0.01). Fourteen days after PTU treatment ended, serum thyroxine did not differ (P = 0.53) among the three respective groups (71.4,73.3, and 57.5 +/- 11.8 ng/mL). Ewes receiving PTU tended to weigh less on d 42 (84.2, 78.2, and 71.8 +/- 5.1 kg for ewes treated with 0, 20, and 40 mg PTU/kg, respectively; linear effect, P = 0.10). Day of onset of anestrus was designated as the day on which serum progesterone decreased and remained below 1 ng/mL. Ewes treated with 0, 20, or 40 mg of PTU/kg BW became anestrous on d 16,40, and 81 (+/- 12) of the experiment, respectively (linear effect, P < 0.01). At the time the 35-d treatment period ended, 25, 60, and 100% of ewes receiving 0, 20, or 40 mg of PTU/kg exhibited normal estrous cycles. In Exp. 2, ewes received 0, 20, or 40 mg of PTU/kg BW for 14 d. The dose was then decreased to 0, 10, and 20 mg of PTU/kg BW for the remaining 21 d. Serum thyroxine decreased to concentrations below 20 ng/mL by d 9 after initiation of PTU treatment. Ewe weights did not differ throughout the trial and no BW loss was observed. The average day that each group entered anestrus was similar to those in Exp 1. Large doses of PTU dramatically lower serum thyroxine and this effect appears to inhibit onset of anestrus in ewes.

Serum thyroid hormones and reproductive characteristics of Rambouillet ewe lambs treated with propylthiouracil before puberty.

Twenty-four Rambouillet ewe lambs (average weight=43.7+/-1.2 kg, approximately 6 months of age) were used to examine the effect of thyroid suppression before the onset of puberty on serum thyroid hormones, body weights (BW), and reproductive performance. Beginning in early September, ewe lambs were randomly assigned to three treatments (n=8 lambs/treatment). All animals remained in a single pen (4 x 12 m) with access to salt, water, shade and alfalfa hay (2.5 kg per animal per day) throughout the experiment. Beginning on Day 0 (first day of treatment), all ewe lambs received daily treatments (gavage) for 15 days consisting of 0, 20, or 40 mg 6-N-propyl-2-thiouracil(PTU)/kg BW per day. Beginning on Day 15, the 20 and 40 mg treatments were lowered to 10 and 20 mg PTU/kg BW, respectively. All animals were treated for 28 days. Ovarian cyclicity was determined by twice weekly progesterone (P(4)) analysis. Thyroxine (T(4)) concentrations were similar on Day 0 (61.6, 54.8 and 56.9+/-2.5 ng/ml, P=0.17) in ewe lambs receiving 0, 20 and 40 mg PTU/kg BW, respectively. By Day 7, both PTU-treated groups had T(4) values less than 20 ng/ml (9.0 and 15.4+/-2.5 ng/ml) compared with 78.5 ng/ml in controls (P<0.01). By 7 days after termination of PTU treatment, serum T(4) had risen to 29.1 and 26.9 (+/-2.9)ng/ml in the 20/10 and 40/20 PTU groups, respectively. On Day 66, control ewes had 55.0 ng T(4)/ml compared with 43.1 and 39.0 (+/-2.6 ng/ml) for ewes in the 20/10 and 40/20 groups, respectively (linear, P<0.01). Serum triiodothyronine (T(3)) followed a similar pattern to that observed for T(4). Ewe lamb BW were similar (P>0.50) among groups throughout the treatment period. However, following the treatment, PTU-treated ewes tended (P<0.10) to weigh less than controls. Average Julian day of puberty was also similar (P>0.50) among treatments (286, 288 and 288+/-5 days; control, 20/10 and 40/20, respectively). Control ewes had a pregnancy rate of 75%, while both PTU-treated groups had pregnancy rates of 88% (P>0.20). The administration of PTU resulted in a rapid decline in serum T(4) and T(3) but neither time of puberty nor pregnancy rates were affected by lowered thyroid hormones.

On the need for monitor unit calculations as part of a beam commissioning methodology for a radiation treatment planning system.

This paper illustrates the need for validating the calculation of monitor units as part of the process of commissioning a photon beam model in a radiation treatment planning system. Examples are provided in which this validation identified subtle errors, either in the dose model or in the implementation of the dose algorithm. These errors would not have been detected if the commissioning process only compared relative dose distributions. A set of beam configurations, with varying field sizes, source-to-skin distances, wedges, and blocking, were established to validate monitor unit calculations for two different beam models in two different radiation treatment planning systems. Monitor units calculated using the treatment planning systems were compared with monitor units calculated from point dose calculations from tissue-maximum ratio (TMR) tables. When discrepancies occurred, the dose models and the code were analyzed to identify the causes of the discrepancies. Discrepancies in monitor unit calculations were both significant (up to 5%) and systematic. Analysis of the dose computation software found: (1) a coordinate system transformation error, (2) mishandling of dose-spread arrays, (3) differences between dose calculations in the commissioning software and the planning software, and (4) shortcomings in modeling of head scatter. Corrections were made in the beam calculation software or in the data sets to overcome these discrepancies. Consequently, we recommend incorporating validation of monitor unit calculations as part of a photon beam commissioning process.

Comparison between TG-51 and TG-21: Calibration of photon and electron beams in water using cylindrical chambers.

A new calibration protocol, developed by the AAPM Task Group 51 (TG-51) to replace the TG-21 protocol, is based on an absorbed-dose to water standard and calibration factor (N(D,w)), while the TG-21 protocol is based on an exposure (or air-kerma) standard and calibration factor (N(x)). Because of differences between these standards and the two protocols, the results of clinical reference dosimetry based on TG-51 may be somewhat different from those based on TG-21. The Radiological Physics Center has conducted a systematic comparison between the two protocols, in which photon and electron beam outputs following both protocols were compared under identical conditions. Cylindrical chambers used in this study were selected from the list given in the TG-51 report, covering the majority of current manufacturers. Measured ratios between absorbed-dose and air-kerma calibration factors, derived from the standards traceable to the NIST, were compared with calculated values using the TG-21 protocol. The comparison suggests that there is roughly a 1% discrepancy between measured and calculated ratios. This discrepancy may provide a reasonable measure of possible changes between the absorbed-dose to water determined by TG-51 and that determined by TG-21 for photon beam calibrations. The typical change in a 6 MV photon beam calibration following the implementation of the TG-51 protocol was about 1%, regardless of the chamber used, and the change was somewhat smaller for an 18 MV photon beam. On the other hand, the results for 9 and 16 MeV electron beams show larger changes up to 2%, perhaps because of the updated electron stopping power data used for the TG-51 protocol, in addition to the inherent 1% discrepancy presented in the calibration factors. The results also indicate that the changes may be dependent on the electron energy.

Use of a multileaf collimator as a dynamic missing-tissue compensator.

A dynamic multileaf collimator (D-MLC) was used to investigate the feasibility of producing missing-tissue compensators. The modulation of the x-ray field in two dimensions produced by conventional physical compensators was mimicked by delivering a sequence of D-MLC-shaped subfields. A method is introduced to calculate monitor units (MU) for dynamically compensated fields that is analogous to and expands upon methods used for conventional compensating filter MU calculations. In this investigation, the tissue deficit at the surface of an anatomical phantom was measured using a Moiré camera. The tissue deficit data were used to generate a series of D-MLC subfields that, delivered in sequence, provided the compensated treatment. Film was used to integrate the dose delivered to a specified depth of compensation. Isodose distributions were measured for uncompensated fields, fields compensated with a conventional lead or plastic filter, and fields compensated with the D-MLC. A comparison of the dose distributions shows the compensation achieved with the dynamic compensating filter is comparable to that achieved using conventional physical compensating filters.

Potential and limitations of invariant kernel conformal therapy.

A treatment planning methodology was developed to investigate the invariant kernel form of conformal therapy proposed by Brahme. Three-dimensional dose distributions were calculated by convolving a rotationally symmetric, invariant kernel with weighting distributions. Fourier transform convolution techniques implemented on an array processor were used to achieve high calculation speeds, thereby allowing iterative techniques in the spatial and frequency domains for computing dose distributions that asymptotically approach a desired dose distribution. To use rotationally symmetric kernels, the generality of the solution is traded for a fast, deterministic, inverse planning approach. The limitations imposed on the dose distributions by this loss of generality are characterized and tentative conclusions are drawn about the potentials and limits of clinical application of this form of the methodology. Further developments of the concept are suggested.

Rotational kernels for conformal therapy.

Conformal therapy treatment planning involves determining an irradiation strategy to deliver a dose distribution which is optimized for a given tumor volume. A technique proposed by Brahme restricts the search for the optimal treatment strategy to x-ray distributions in which points within the target volume are irradiated uniformly under rotation of the beam source around the patient. The dose distribution in this case may be calculated as a convolution of an irradiation weighting distribution with an invariant kernel. A procedure is described for calculating three-dimensional kernels to be used for clinical treatment planning with x rays produced by an electron accelerator. The convolution kernel is calculated as the sum of pencil beams irradiating the center of a cylindrical phantom uniformly from all angles. The shape of the kernel at points off the center of the phantom is investigated by means of numerical calculations which support the assumption that the kernel is invariant with respect to position within the phantom. The calculated kernels are verified by comparison with experimentally measured rotational arc dose distributions.