Total Dose Range Research Articles

Bystander and delayed effects after fractionated radiation exposure.

Human immortalized keratinocytes were exposed to a range of single or fractionated doses of gamma rays from (60)Co, to medium harvested from donor cells exposed to these protocols, or to a combination of radiation and irradiated cell conditioned medium (ICCM). The surviving fractions after direct irradiation or exposure to ICCM were determined using a clonogenic assay. The results show that medium harvested from cultures receiving fractionated irradiation gave lower "recovery factors" than direct fractionated irradiation, where normal split-dose recovery occurred. The recovery factor is defined here as the surviving fraction of the cells receiving two doses (direct or ICCM) separated by an interval of 2 h divided by the surviving fraction of cells receiving the same dose in one exposure. After treatment with ICCM, the recovery factors were less than 1 over a range of total doses from 5 mGy-5 Gy. Varying the time between doses from 10 min to 180 min did not alter the effect of ICCM, suggesting that two exposures to ICCM are more toxic than one irrespective of the dose used to generate the response. In certain protocols using mixtures of direct irradiation and ICCM, it was possible to eliminate the bystander effect. If bystander factors are produced in vivo, then they may reduce the sparing effect of the dose fractionation.

T1 stage breast cancer: adjuvant hypofractionated conformal radiation therapy to tumor bed in selected postmenopausal breast cancer patients--pilot feasibility study.

To explore the feasibility of a short course of hypofractionated conformal radiation therapy to the tumor bed as part of a breast preservation protocol in postmenopausal patients with nonpalpable pT1N0 stage breast cancer. The tumor bed was imaged at computed tomography (CT) in the prone position on a dedicated table. The same table and position were used for treatment with a 4-MV linear accelerator. The planning target volume was the tumor bed plus a 1-2-cm margin defined at postmastectomy CT. A regimen of five fractions was tested in this pilot dose study. Cosmesis was assessed by patients and physicians before treatment and 36 months after treatment. Ten consecutive patients who were eligible for the study were assigned to one of three dose-per-fraction regimens; nine were treatable with the proposed technique on the basis of CT findings. Patients received five fractions over 10 days (total dose range, 25-30 Gy): Three received 5.0 Gy per fraction; four, 5.5 Gy; and two, 6.0 Gy. At minimum follow-up of 36 months (range, 36-53 months), all patients were alive and disease free with good to excellent cosmesis. Hypofractionated conformal breast radiation therapy is feasible. Further studies are warranted.

Radiation prophylaxis for heterotopic ossification about the hip joint—a multicenter study

Purpose: Prophylactic radiotherapy (RT) can prevent ectopic bone formation about the hip after total hip arthroplasty. The German Cooperative Group on Radiotherapy for Benign Diseases conducted a patterns of care study about this indication addressing the involved institutions, RT dose concepts, clinical handling, and treatment outcome of prophylactic RT about the hip joint.Methods and Materials: In 1999, a patterns of care study was conducted in all German institutions to analyze the accrual pattern, number of patients, and different indications for the use and performance of prophylactic RT about the hip. The applied RT concepts of prophylactic RT were evaluated with regard to the RT technique, timing of RT (pre- or postoperative), RT dose prescription (median, range of single and total doses), and treatment outcome. All institutions were asked about the radiologic and functional failure rates at least 1 year after the completion of RT using the established radiologic (Brooker) and functional (Harris) scores with objective and subjective evaluation components.Results: One hundred fourteen institutions reported their clinical experience with prophylactic RT for the prevention of heterotopic ossification about the hip joint: 70 community hospitals, 23 university hospitals, and 21 private RT practices. In 1999, 5677 patients (5989 hips) had received prophylactic RT. The median number per institution was 36 patients (range 8–240). The interdisciplinary referral included orthopedic surgery (89 institutions; 3763 patients), trauma surgery (82 institutions; 1611 patients), or other disciplines (8 institutions; 298 patients). Preoperative RT was applied in 53 institutions 0.5–24 h before surgery, and postoperative RT was applied in 54 institutions 1–120 h after surgery. Most patients received 1 × 7 Gy either pre- or postoperatively. The total dose range was 5–10 Gy (preoperative RT) or 5–16 Gy (postoperative RT); the median total RT dose of both RT concepts was 7 Gy. Cobalt-60 (n = 15), linear accelerators (n = 95), and a few lower energy units (n = 4) were used. Bony structures or prostheses were shielded with standard blocks in 31 and with individual blocks in 27 institutions. Long-term clinical evaluation was available in 30 institutions from 4377 hips. Of those, 475 (11%) developed radiologic failures according to Brooker’s criteria. Functional hip evaluation was available in 5 institutions from 685 hips. Of those, 34 (5%) had functional failures according to the criteria of Harris. No difference in outcome was found between pre- and postoperative RT, but was with regard to the patient’s referral and the timing of RT. The patients who were treated >8 h before surgery or >72 h after surgery experienced a higher radiologic failure rate; radiologic failures were an important precondition for functional failures (p <0.05).Conclusion: This patterns of care study comprises the largest number of cases reported for prophylactic hip RT to date. The results reveal that both preoperative (within 24 h) and postoperative RT (within 72 h) are effective in preventing heterotopic ossification after hip surgery. Both RT concepts achieved a similar low radiologic and functional failure rate. Single-dose RT concepts, especially, can be recommended as an excellent treatment alternative for patients with contraindications to long-term steroid or nonsteroidal anti-inflammatory agents, and this approach has become standard in most German RT institutions.

Kaplan‐Meier Tumor Probability as a Starting Point for Dose‐Response Modeling Provides Accurate Lifetime Risk Estimates from Rodent Carcinogenicity Studies

In rodent carcinogenicity studies the linearized multistage model for modelling the dose-response for specific tumor incidence has limitations in accuracy. This note provides an alternative basic method for analyzing the dose-response relationship. It is based on an actuarial analysis of mortality and specific tumor incidence. The survival and the Kaplan-Meier specific tumor probability are fitted to a Weibull model, in which exposure level, exposure period, and observation period are independent variables. The mortality from specific cancers at a certain time is simulated by means of the product of survival and specific tumor rate (derivative of Kaplan-Meier tumor probability) as function of exposure level, exposure duration, and observation period, integrated over the observation period. The model is demonstrated by means of fitting the mortality and tumor incidence data from the second NTP mice study on butadiene to a Weibull model and to the linear, so-called, one-hit model. It will be shown that, in the experimental exposure range, the Weibull model is far superior to the one-hit model and predicts the specific tumor incidence with a high accuracy over the total dose range. The Kaplan-Meier probability model for a specific tumor is also useful for regulatory risk estimation. It is proposed that to develop a specific tumor a risk level of 1 in 1,000 over a lifetime is about equal to 5 in 10,000 at 50% survival of the population. The Kaplan-Meier probability may be estimated at the time of 50% survival of the exposed population, which can be deduced from the all mortality data. This estimation method provides meaningful data, using exposure level, exposure duration, and observation period properly. The advantage of the actuarial analysis method for interpreting rodent studies is that allowance is made for competition between death causes, which is essential in case of considerable difference in mortality and specific mortality between dose groups. Integrating the product of survival and specific tumor rate is the proper way to predict, comparatively, mortality and specific mortality in exposed and unexposed rodent populations.

Intravenous midazolam for sedation of children undergoing procedures: an analysis of age- and procedure-related factors.

This study was performed to determine the doses of midazolam used for sedation during procedures in children, and the frequency of adverse events. We performed a retrospective analysis of data collected for a prospective study of flumazenil in children who had received midazolam for a procedure (n = 91, 1-17 years). Practitioners used a wide range of total midazolam doses (0.03-0.6 mg/kg); mean doses ranged from 0.09 +/- 0.06 mg/kg in adolescents to 0.26 +/- 0.13 mg/kg in toddlers (P < 0.001). Opioids were also used in 84% of patients. Twenty-six percent of children with normal lungs, most of whom had received relatively high opioid doses, developed decreased oxygen saturation (as low as 65%) after sedation. Other adverse events included airway obstruction (n = 3) and vomiting (n = 1). The frequent choice of midazolam, usually combined with an opioid, indicates its wide acceptance. Midazolam doses were inversely related to age. The presence of vomiting, airway obstruction, and decreased oxygen saturation underlines the importance of appropriate personnel, equipment, and monitors during sedation.

Technical management of a pregnant patient undergoing radiation therapy to the head and neck

The fetal dose in a pregnant patient undergoing radiation therapy to the head and neck region was investigated. Implicit in this study was the design and evaluation of a shield used to minimize the fetal dose. To evaluate the fetal dose, a phantom was irradiated with the fields designed for this patient’s therapy. The peripheral dose was measured for each field individually, both without and with a custom shield designed to be placed about the patient’s abdominal and pelvic regions. The total dose at the location of the fetus over the course of this patient’s radiation therapy was then estimated from peripheral dose rate measurements made at several points within the simulated uterus. With no shielding, the total dose within the uterus of the patient would have ranged from 13.3 cGy at the cervix to 28 cGy at the fundus. With the shield applied, the uterine dose was significantly less: 3.3 cGy at the cervix to 8.6 cGy at the fundus. In fact, at every measurement point, the peripheral dose with the shield in place was 30% to 50% of the dose without the shield. Some data suggest that the rate of significant abnormalities induced by irradiation in utero increases with increasing dose within the range of total peripheral doses incurred during most radiation treatment courses. It is therefore prudent to make reasonable attempts at minimizing the dose to the lower abdominal and pelvic regions of any pregnant patient. The shield designed in this work accomplished this goal for this patient and is flexible enough to be used in the treatment of almost all tumor volumes.

Dose-depth and SEU monitors for the STRV-1c satellite

Small, low power instruments have been developed to monitor total-dose and single event upsets (SEUs) in spaceborne electronics. These instruments have been designed to act as continuous monitors on the Science and Technology Research Vehicle (STRV) satellite. They will also act as monitors for other spacecraft in orbits where total dose, single event upsets (SEUs) and other single event effects (SEEs) are considered a significant hazard to on-board electronics. Flight Models of each instrument have been designed and built to interface with the satellite on-board computer. The instruments have been characterized over the total dose range of 100 rads to 100 krads and the proton energy range 10 MeV to 500 MeV. The proton SEU cross section of 2/spl times/10/sup -11/ cm/sup 2//bit is orders of magnitude more sensitive to protons than current flight electronics components. These instruments will be flown on the STRV-1c satellite in a Geosynchronous Transfer Orbit (GTO).

Total dose radiation hard 0.35 /spl mu/m SOI CMOS technology

This paper presents the total dose radiation performance of 0.35 /spl mu/m SOI CMOS devices fabricated in a radiation hard full dose SIMOX technology. The radiation performance is characterized by transistor threshold voltage shifts, transistor array leakage currents, and 256 K SRAM standby currents as a function of total dose up to 10 Mrad(SiO/sub 2/). The worst case threshold voltage shifts of front channels are less than 60 mV for PMOS transistors at 1 Mrad(SiO/sub 2/) and less than 10 mV for NMOS transistors. No significant radiation induced leakage currents are observed in small transistor arrays to 10 Mrad(SiO/sub 2/). Standby currents of 256 K SRAMs are less than the 1.5 mA specification over the total dose range of 1 Mrad(SiO/sub 2/). The results suggest high density SRAMs and ASIC fabricated in this technology will perform well in harsh radiation environment.

Superior vena cava obstruction in small-cell lung cancer

To identify prognostic or treatment factors influencing the response of superior vena cava obstruction (SVCO), time to SVCO recurrence, and overall survival of SCLC patients with SVCO at presentation; and to assess the role of retreatment in patients with SVCO at recurrent or persistent disease. Between January 1983 and November 1993, 76 consecutive patients who had small-cell lung cancer (SCLC) with SVCO were treated in our institution. Analysis was done according to the disease status at diagnosis of SVCO. The first analysis concerned a group of 50 patients who had SVCO at initial presentation. The second analysis concerned a group who had SVCO as a manifestation of persistent or recurrent disease. In the first analysis, 93% had significant improvement in symptoms of SVCO after chemotherapy and 94% after mediastinal radiation. Response is almost universal despite a wide range of radiation fractionation and total dose used. Seventy percent remained SVCO-free before death. Thirty percent developed recurrence of SVCO symptoms 1-16 months (median 8) after the start of initial treatment. Those who received combined chemotherapy and radiation had a longer time to SVCO recurrence (p = 0.018) compared to those who received chemotherapy alone. This effect is mainly seen in limited-stage patients. The presence of SVCO recurrence tends to have an adverse effect on the overall survival (p = 0.077) irrespective of the time when the recurrences occurred (p = 0.296). The median survival of this whole group of 50 patients in the first analysis was 9.5 months, and the 2-year survival was 10%. Stage was strongly predictive of survival (p < 0.001). Sixteen percent (3 of 19) of the patients with limited-stage diseases were long-term survivors (two patients survived 35 months and one survived 70 months). The early mortality from SVCO was 2%. In the second analysis, 85% had previously been treated with chemotherapy alone. The response rate of SVCO in the analysable patients (n = 39) was 77%. There was no significant difference in the response rate of SVCO to treatment comparing patients treated by chemotherapy first or mediastinal radiation first (p = 0.653), but most patients [82% (32 of 39)] received radiation as the initially treatment of SVCO. Ninety-three percent (38 of 41) received mediastinal radiation as a part of their ultimate retreatment regimen, and 68% (28 of 41) received mediastinal radiation as their sole retreatment regimen. Thirty-two percent (13 of 41) received chemotherapy as a part of their ultimate retreatment regimen, and only 7% received chemotherapy alone as their sole retreatment regimen. Eighty-three percent (25 of 30) of those whose SVCO responded remained free of SVCO before death, with a median survival of 3 months after recurrent or persistent disease documented. Chemotherapy or mediastinal radiation is very effective as an initial treatment in SCLC patients with SVCO at presentation and at recurrent or persistent disease. There is no obvious need to use big radiation fraction sizes for the first few radiation treatment as was previously believed. In patients with recurrent or persistent SCLC with SVCO, especially in those who previously received chemotherapy only, we have more experience in incorporating mediastinal radiation as a major component of the palliative regimen with highly effective and durable palliation achieved.

Impact of radiation therapy fraction size on local control of early glottic carcinoma

Purpose : Different radiotherapy fractionation schedules were used over a 10-year period to treat patients with early squamous cell carcinoma of the vocal cords at McGill University. A retrospective analysis was performed to study the effect of fraction size on local control in this group of patients. Methods and Materials : A total of 126 previously untreated patients with T1 invasive squamous cell carcinoma of the true vocal cords were irradiated between January 1978 and December 1988 in the Department of Radiation Oncology at McGill University. All patients received megavoltage irradiation, 94 patients received daily fractions > 2 Gy (64 patients received 50 Gy with once-daily 2.5-Gy fractions, and 30 received 65.25 Gy in 29 fractions of 2.25 Gy each), and 32 patients were treated to a dose of 66 Gy in 33 fractions with 2 Gy/fraction. Patients' characteristics of prognostic importance were equally distributed between the two fractionation groups. Results : At a median follow-up of 84 months, the 10-year disease-free survival and overall survival were 76% and 93%, respectively. Local control for patients treated with > 2 Gy fraction was 84%, compared to 65.6% for those treated with 2-Gy fractions ( p = 0.026). Among the prognostic factors tested, such as gender, age, stage, anterior and posterior commissure involvement, smoking history, and fraction size, the latter was the only significant predictor of local control for the whole group of patients in univariate ( p = 0.041) and multivariate ( p = 0.023) analysis. There was no observed difference in the incidence of complications between the two fractionation groups. Conclusions : From the results of this retrospective review of patients treated with radiotherapy for T1 true vocal cord cancer, and within the range of total doses and overall treatment times used in our patients, it was found that fractionation schedules using daily fraction size > 2 Gy are associated with a better local control than schedules delivering 2 Gy/fraction, with no increase in toxicity.

Radioactivity in two tide-washed marsh areas in the eastern Irish Sea: a radiological assessment

The doses received by man from exposure to artificial radionuclides deposited onto marsh land during tidal inundation on the English side of the Solway Firth and the Dee Estuary have been assessed. The range of total doses received by the different marsh user groups was similar in both study areas, varying from <1 μSv year−1 to ∼55 μSv year−1, with total dose dominated by the contribution from external exposure (generally 80% of the total). The maximum doses in both study areas were received by people working on the marshes and are well below the annual dose limit recommended by ICRP for members of the public (1 mSv year−1. The largest dose estimated (56 μSv year−1 is only 6% of the recommended dose limit.

Sodium Nitroprusside

Sodium Nitroprusside

1031–33 Intravenous Triiodothyronine in Patients with Advanced Heart Failure

Thyroid hormone metabolism is frequently abnormal in patients with advanced congestive heart failure (CHF), with low triiodothyronine (T3) levels associated with poor hemodynamics and increased mortality. Studies have suggested that intravenous (i.v.) T3 improves hemodynamics acutely in patients immediately post-bypass surgery. To assess the safety of i.v. T3 (which may have unique inotropic mechanisms) in CHF, 22 patients with class III or IV CHF were given an Lv. T3 bolus ± 6 hour infusion (total dose range 0.05 – 1.7 /.μg/kg) under hemodynamic and ECG monitoring. Basal metabolic rate (BMR) by indirect calorimetry and LVEF by echo were measured at baseline and 2–4 hours post dosing. No patient had angina or sustained supraventricular or ventricular ectopy and mean heart rate (HR) did not change significantly (94 ± 16 to 98 ± 13 bpm, p = NS), with only 3/22 patients having an increase in HR &gt; 10 bpm. There was no significant change in mean BMR (2221 ± 899 to 2449 ± 682 Kcal/day, p = NS) and only minimal change in mean core temperature (36.8 ± 0.4 to 37.3 ± 0.6°C, P = 0.007), reflecting a peak temperature 38.0–38.5°C in 4 patients. Cardiac output increased by &gt; 1.0 L/mm in 11/22 patients (&gt;50% increase over baseline in 8/22 patients) with no significant change in LVEF (22 ± 7 to 23 ± 6%, P = NS) or filling pressures. Acute intravenous T3 administration is well tolerated in patients with advanced CHF and has potential hemodynamic benefit warranting further investigation.

The effect of irradiation on expression of HLA class I antigens in human brain tumors in culture

The immunosuppressive effects of irradiation are well known; however, under certain circumstances irradiation also augments the local immune response by as yet undefined mechanisms. Because of the importance of HLA class I antigen in immune regulation and the fact that killing of tumor cells by cytotoxic T cells is HLA antigen-restricted, the authors studied HLA class I antigen expression in eight glioblastomas multiforme, four meningiomas, and four medulloblastomas. Twenty fragments of each tumor specimen were placed in short-term cultures immediately after resection. For each tumor, control Sample 1 was not irradiated. Sample 2 was irradiated on Day 1, and two groups of the remaining pieces of each tumor (specimens 3 to 10) were irradiated on two consecutive days. Escalating radiation doses were given, starting at 200 cGy/day for Sample 2 up to 1000 cGy/day for Sample 10. The total dose range was 200 to 2000 cGy. Corresponding nonirradiated tumor fragments served as controls. Four hours after irradiation, each sample was processed and stained for HLA class I antigen using the immunoperoxidase technique. The tumor cells were intensely stained in nonirradiated glioblastomas and meningiomas, whereas no staining was observed in medulloblastomas. In four of the eight glioblastomas and in all four meningiomas, irradiation augmented HLA class I antigen expression compared to controls. This effect was dose-dependent and was maximum in the 1200 cGy-treated specimens. No change was observed in the other four glioblastomas or in the medulloblastomas. The data suggest that irradiation does not decrease and may even induce HLA class I antigen expression in some brain tumors. This may be one of the mechanisms by which immunotherapy operates after irradiation. Further studies are required to elucidate optimum radiation doses and fractionation as well as optimum timing of immunotherapy.

Effect of ICI197067, a κ-opioid receptor agonist, spinally on Aδ and C reflexes and intracerebrally on respiration

Intrathecal (i.t.) injection of a κ-opioid receptor agonist, ICI197067, caused a similar dose dependent depression of Aδ and C fibre mediated nociceptive reflexes in renal sympathetic nerves due to supramaximal electrical stimulation of tibial nerves in anaesthetized dogs. A total dose of 8 mg i.t. abolished these reflexes. When administered into the 4th ventricle (i.c.v.) in a total dose range from 0.1–2.5 mg ICI197067 caused no respiratory depression; a total dose of 10 mg i.c.v. abolished both phrenic nerve activity and spontaneous respiration. The ED 50 ratio of ICI197067 for depression of respiration (i.c.v.) and somatosympathetic reflexes (i.t.) is approximately 1.5:1 compared with 0.3:1 for fentanyl. ICI197067 i.c.v. caused a similar reduction in arterial pressure compare to fentanyl without comparable changes in heart rate. Thus in terms of cardiorespiratory depression and blockade of Aδ and C fibre pathways κ-opioid receptor agonists may be safer and more effective for producing spinal analgesia than μ-opioid receptor agonists.

Radiation Pneumonitis in Rats and Its Modification by the Angiotensin-Converting Enzyme Inhibitor Captopril Evaluated by High-Resolution Computed Tomography

Adult male Sprague-Dawley rats were irradiated to the right hemithorax with a range of total doses delivered in 10 equal daily fractions of 4 MeV X rays. Half of each dose group consumed control feed, and half consumed feed containing the angiotensin-converting enzyme inhibitor captopril (50 mg/kg/day) continuously after the last irradiation. High-resolution computed tomography (CT) of the entire thorax was performed at 4 and 8 weeks after the last irradiation, and the findings with CT were correlated with hemodynamic data, heart weight, and pulmonary histopathology. Rats exposed to 20 or 40 Gy in 10 fractions exhibited no acute changes in right lung density. After 60 Gy in 10 fractions, however, right lung density in rats on the control diet increased significantly at 4 weeks, and then returned to normal at 8 weeks. Captopril-treated rats exposed to 60 Gy/10 fractions did not exhibit this transient increase in right lung density. After 80 Gy/10 fractions, right lung density increased to 0.60-0.65 g/cm3 at 4 weeks regardless of diet. At 8 weeks after 80 Gy/10 fractions, right lung density increased further in rats given the control diet, but decreased to near normal levels in captopril-treated animals. The density of the shielded left lung based on the CT was independent of both contralateral radiation dose and diet. Histological examination of the irradiated lungs indicated that these acute changes detected by CT were associated with the exudative and edematous phases of radiation pneumonitis, and that captopril reduced the severity of these changes. Irradiated (40-80 Gy/10 fractions) animals fed the control diet exhibited a significant increase in central venous and pulmonary artery pressure, and cardiac right ventricular hypertrophy. Captopril prevented or attenuated these hypertensive reactions. These data demonstrate that high-resolution CT can detect radiation reactions in rat lung within 4 weeks after 60 Gy/10 fractions, and that captopril spares these acute changes detected by CT. The mechanism of captopril action is not clear, but may be due in part to a reduction in pulmonary arterial pressure, resulting in less severe edema in the irradiated lung.

Low dose rate teletherapy and tumour response

Tumour responses in 25 patients with locally advanced head and neck cancer, treated on an experimental fractionated low dose rate (FLDR) teletherapy program are reported. Treatment was given at dose rates ranging from 1.8 to 3 Gy/h to a range of total doses from 32-38 Gy, with palliative intent. The total doses delivered have been predicted by the linear quadratic formula to be equivalent to 33-41 Gy using conventionally fractionated high dose rate treatment, in terms of acute normal tissue effects. A complete response rate (no visible or palpable disease 2 months after treatment) was observed in 28% of cases. Analysis of these response rates suggests that the linear quadratic formula may underestimate the anti-tumour effect of FLDR teletherapy at the various dose rates and total dose permutations in this study.

Fractionation sensitivity and latency of late radiation injury to the mouse urinary bladder

Transurethral bladder filling is a functional, non-invasive, in vivo assay of early and late radiation injury to the mouse bladder. Fractionated irradiations using single doses or 2, 3, 5, or 10 dose fractions in an overall time of 4 or 4.5 days, with a range of total doses, were given to the bladder of 12–14 week-old C 3D 2F 1/Bom mice. In 372 mice, bladder volume at an intravesical pressure of 20 mmHg was measured before irradiation and at regular intervals thereafter. The endpoint for late bladder injury was a volume of less than 50% of the median pretreatment volume in all animals, occurring more than 30 days after irradiation. This endpoint was reached after a latent period ranging between 35 and 401 days. Fractionation and latency parameters were estimated using a mixture model. There was a highly statistically significant dose-dependency of the latent period ( p < 10 −8). The α β ratio was estimated at 5.8 Gy [95% confidence limits (3.6; 8.8) Gy] for 250 kVp X-rays. Thus late radiation injury in the mouse urinary bladder is one of the least sensitive late endpoints with respect to change in dose per fraction. Introducing early bladder injury as a variable in the model improved the fit significantly ( p = 0.03), but the α β ratio remained unchanged. Thus the hypothesis that late bladder injury may be, at least in part, consequent upon early injury did not explain the relatively high α β ratio for this late endpoint.

Cerebral Blood Flow Measurements During Blood Pressure Control with Intravenous Labetalol Following Craniotomy

Cerebral blood flow measurements using a thermal diffusion technique were made in conjunction with an extensive cardiovascular evaluation, during and after administration of intravenous labetalol given for blood pressure control in craniotomy patients. Eighteen patients, ages 30-65 years, ASAII and III, scheduled for elective craniotomy, became hypertensive during emergence and recovery from a pentothal/fentanyl/vecuronium/N2O/isoflurane general anesthesia. Labetalol was administered in a stepwise manner every 10 minutes during an average period of 1 h. After this titration period, an 8-h maintenance period followed. During titration and maintenance periods, comprehensive systemic hemodynamic parameters were collected through intra-arterial and flow-directed pulmonary artery catheters. Cerebral cortical blood flow (CBF) was continuously recorded using a thermal diffusion cortical blood flow probe (Saber System). Data were analyzed using variance F tests to evaluate changes from baseline over time. Labetalol controlled postoperative hypertension in all cases with a total dose range of 0.4-6.8 mg/kg. During titration, statistically significant decreases in blood pressure were obtained, accompanied by a small decrease in systemic vascular resistance (SVR) and slight increase in cardiac index (CI). Heart rate decreased in a manner directly proportional to the dose of labetalol administered. In the maintenance period, further decreases in blood pressure and heart rate were observed, with significant decreases in central venous pressure, pulmonary capillary wedge pressure, and SVR and an increase in CI. All values remained within normal ranges and no adverse effects were observed. CBF decreased slightly during the study period, although not significantly (from 67 +/- 8 to 57 +/- 7 ml 100 g min). Blood pressure control achieved with labetalol in postoperative neurosurgical patients seems to be the result of mild alpha-adrenoceptor blocking effects (i.e., reduced SVR) and beta-adrenoceptor blocking effects (i.e., reduced heart rate) at higher doses. The 6-8 h duration of effect of labetalol was enough to control postoperative hypertension in all patients with no additional therapy. Compared with alternative drugs available for blood pressure control in similar clinical conditions, labetalol appears to be reliable, safe, and effective, by providing a lasting effect with no evidence of rebound hypertension, increased CBF, or cardiac dysfunction.

Germination of seeds from an irradiated forest: Implications for waste disposal

Jack pine ( Pinus banksiana Lamb.) retain their seeds from year to year, so that in an irradiated forest, each tree receives a specific dose rate but has seeds that have accumulated a range of total doses. The Field Irradiator-Gamma facility in Pinawa, Manitoba, contains jack pine that have been irradiated longer and at lower dose rates than previously reported. Seed germination and germination rate were examined on seeds irradiated on the parent tree for up to 5 years. Germination rate was most sensitive and showed deleterious effects at 1.1 mGy hr −1. This is not much lower than results reported by others in shorter-term studies. Effects were related to dose rate rather than total dose. Hormesis, indicated by statistically significant increased germination rate, was evident at 0.6 mGy hr −1. To put these results into context, the concentrations of selected radionuclides that, through internal contamination, would deliver 1.1 mGy hr −1 to plants were estimated. For 99Tc and 129I, these concentrations are far above the chemical toxicity thresholds for plants. Clearly, as assessments of waste repositories begin to consider effects on organisms other than humans, such as plants, chemical toxicity will be an important feature.