Nonopioid Pain Management Pathways for Stone Disease.

Introduction: New opioid dependency after urologic surgery is a serious adverse outcome that is well-described in the literature. Patients with stone disease often require multiple procedures because of recurrence of disease and hence are at greater risk for repeat opioid exposures. Despite this, opioid prescribing after urologic surgery remains highly variable and in an emergency setting, opioids are still used commonly in management of acute renal colic. Methods: Two literature searches were performed using PubMed. First, we searched available literature concerning opioid-sparing pathways in acute renal colic. Second, we searched available literature for opioid-sparing pathways in ureteroscopy and percutaneous nephrolithotomy (PCNL). Abstracts were reviewed for inclusion in our narrative review. Results: In the setting of acute renal colic, multiple randomized control trials have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) attain greater reduction in pain scores, decreased need for rescue medications, and decreased vomiting events in comparison with opioids. NSAIDs also form a core component in management of postureteroscopy pain and have been demonstrated in randomized trials to have equivalent to improved pain control outcomes compared with opioids. Multiple opioid-free pathways have been described for postureteroscopy analgesia with need for rescue narcotics falling under 20% in most studies, including in patients with ureteral stents. Enhanced Recovery After Surgery protocols after percutaneous nephrolithotomy are less well described but have yielded a reduction in postoperative opioid requirements. Conclusions: In select patients, both acute renal colic and after kidney stone surgery, adequate pain management can usually be obtained with minimal or no opioid medication. NSAIDs form the core of most described opioid-sparing pathways for both ureteroscopy and PCNL, with the contribution of other components to postoperative pain outcomes limited because of lack of head-to-head comparisons. However, medications aimed specifically at targeting stent-related discomfort form a key component of most multimodal postsurgical pain management pathways. Further investigation is needed to develop pathways in patients unable to tolerate NSAIDs.

The Role of Alumni Networks and Career Advising in Early Career Stability of Urologists: Results of a Multi-institutional Study.

OBJECTIVE: To characterize training program and early career factors that impact decision-making and job retention following graduation in a diverse population of urologists. MATERIALS AND METHODS: We performed a computer-based survey distributed to residency graduates from 25 urology training programs. Five focus institutions were identified with a goal >30% response rate. The survey included questions about training program specifics and post-training employment characteristics. RESULTS: We obtained 180 responses from urology residency graduates of 25 programs. Overall, 72% (N = 129) remain in their initial post-training position at a median of 6years postgraduation (Interquartile Range (IQR) 3-10). On Cox-regression analysis stronger trainee-rated formal career advising was associated with lower risk of changing jobs (HR 0.77, 0.60-0.99, P = .048). Location/proximity to family was the most consistently cited as the top reason for selecting a job (41%). Sixty-three respondents (35%) joined practices employing graduates of the same residency program. Cox regression analysis showed that joining a practice with alumni of the same program was associated with lower risk of changing jobs from one's initial post-training position (HR 0.39, 95% CI 0.17-0.91, P = .03). CONCLUSION: In this multi-institutional study of urologists, we observed a high rate of job retention out to a median of 6years following completion of training, with formal career advising and joining alumni in practice being associated with job retention. Collectively, our data highlights that training programs should emphasize advising programs and alumni networking in guiding their graduates in the job search process.

Antimicrobial interventions to reduce Salmonella and Campylobacter populations and improve shelf life of quail carcasses.

Quail (Coturnix japonica) is processed and marketed as fresh meat, with limited shelf life. The objective of this study was to evaluate the efficacy of antimicrobial interventions during slaughter on reducing Salmonella and Campylobacter contamination and to determine the microbiological shelf life of quail during refrigerated (4°C) storage. Three antimicrobials, peracetic acid (400 ppm; PAA), Citrilow (pH 1.2), and Cecure (cetylpyridinium chloride [CPC], 450 ppm), along with a water and no-treatment control were evaluated. Quail carcasses (n = 75) were inoculated with a cocktail of nalidixic acid-resistant Salmonella Typhimurium and gentamicin-resistant Campylobacter coli. After 30 min of attachment time, quail carcasses were submerged in each antimicrobial solution for 20 s with air agitation. Noninoculated quail carcasses (n = 25) were similarly treated, packaged, and stored under refrigeration (4°C). Aerobic plate counts (APC), psychrotroph counts (PC), Enterobacteriaceae counts (ENT), total coliform counts (TCC), and Escherichia coli counts on quail carcasses were determined on 1, 4, 7, and 10 d. Salmonella and Campylobacter populations were determined by plating on Petrifilm APC supplemented with 200-ppm nalidixic acid and Campy Cefex agar supplemented with 200-ppm gentamycin, respectively. No significant reductions in (P > 0.01 log cfu/mL) in APC, PC, ENT, TCC, and E. coli counts were observed on carcasses submerged in water. However, treatments with PAA, Citrilow, and CPC significantly reduced (P ≤ 0.05) Salmonella and Campylobacter coli contamination. Citrilow showed greater (P ≤ 0.05) reduction in Salmonella and Campylobacter population (1.90 and 3.82 log cfu/mL reduction, respectively) to PAA and CPC. Greater (P ≤ 0.05) reductions in APC, PC, ENT, TCC, and E. coli counts (2.22, 1.26, 1.47, 1.52, and 1.59 log cfu/mL, respectively) were obtained with the application of CPC. Application of antimicrobial interventions resulted in a reduction in Campylobacter and Salmonella, APC, PC, and ENT populations after treatments (day 0) and throughout the storage period (day 10). Use of antimicrobial interventions after slaughter can improve the microbiological safety and shelf life of quail.

Synaptic elimination and protection after minimal injury depend on cell type and their prelesion structural dynamics in the adult cerebral cortex.

The axonal and synaptic mechanisms underlying dysfunction and repair of the injured CNS are poorly understood. Unresolved issues include to what degree, when, and how the surviving neurons degenerate and the extent of synaptic remodeling both along the severed axon and in the nearby area. One of the main reasons is the lack of tools to study the complex asynchronous and dynamic features of individual lesioned axon responses in the intact brain. To address these issues, we combined two-photon microscopy and laser microsurgery to image the real-time reorganization of cortical circuitry at synaptic resolution for periods of up to 1 year in the brain of living mice. Injured cortical axons were eliminated proximally through a two-phase retraction process, which continued for at least 3 months postlesion and was independent of the presence of scar tissue. Remarkably, axons which later attempt to regenerate in both the mature and juvenile brain retracted less, raising the possibility that targeting retraction may improve the chances of axon regrowth after axotomy. Comparing prelesion and postlesion dynamics on the same axons over several days and weeks revealed that, although synapse formation rates were unaffected, boutons on injured axons were either rapidly and persistently lost, or extremely resistant, depending on cell-type and their prelesion structural dynamics. Our data suggest a lasting deficiency in synaptic output on surviving injured cortical axons and a surprising difference in the vulnerability of synaptic boutons after axotomy, which depend on cell-type and their recent history.

In-vivo single neuron axotomy triggers axon regeneration to restore synaptic density in specific cortical circuits.

To what extent, how and when axons respond to injury in the highly interconnected grey matter is poorly understood. Here we use two-photon imaging and focused ion beam-scanning electron microscopy to explore, at synaptic resolution, the regrowth capacity of several neuronal populations in the intact brain. Time-lapse analysis of >100 individually ablated axons for periods of up to a year reveals a surprising inability to regenerate even in a glial scar-free environment. However, depending on cell type some axons spontaneously extend for distances unseen in the unlesioned adult cortex and at maximum speeds comparable to peripheral nerve regeneration. Regrowth follows a distinct pattern from developmental axon growth. Remarkably, although never reconnecting to the original targets, axons consistently form new boutons at comparable prelesion synaptic densities, implying the existence of intrinsic homeostatic programmes, which regulate synaptic numbers on regenerating axons. Our results may help guide future clinical investigations to promote functional axon regeneration.

The impact of lesion in-painting and registration methods on voxel-based morphometry in detecting regional cerebral gray matter atrophy in multiple sclerosis.

BACKGROUND AND PURPOSE: VBM has been widely used to study GM atrophy in MS. MS lesions lead to segmentation and registration errors that may affect the reliability of VBM results. Improved segmentation and registration have been demonstrated by WM LI before segmentation. DARTEL appears to improve registration versus the USM. Our aim was to compare the performance of VBM-DARTEL versus VBM-USM and the effect of LI in the regional analysis of GM atrophy in MS. MATERIALS AND METHODS: 3T T1 MR imaging scans were acquired from 26 patients with RRMS and 28 age-matched NC. LI replaced WM lesions with normal-appearing WM intensities before image segmentation. VBM analysis was performed in SPM8 by using DARTEL and USM with and without LI, allowing the comparison of 4 VBM methods (DARTEL + LI, DARTEL - LI, USM + LI, and USM - LI). Accuracy of VBM was assessed by using NMI, CC, and a simulation analysis. RESULTS: Overall, DARTEL + LI yielded the most accurate GM maps among the 4 methods (highest NMI and CC, P < .001). DARTEL + LI showed significant GM loss in the bilateral thalami and caudate nuclei in patients with RRMS versus NC. The other 3 methods overestimated the number of regions of GM loss in RRMS versus NC. LI improved the accuracy of both VBM methods. Simulated data suggested the accuracy of the results provided from patient MR imaging analysis. CONCLUSIONS: We introduce a pipeline that shows promise in limiting segmentation and registration errors in VBM analysis in MS.

The relationship between socioeconomic position and depression among a US nationally representative sample of African Americans.

PURPOSE: Findings from previous studies have not revealed significant, inverse relationships between socioeconomic position (SEP) and depression among African Americans. This study examined the relationship between multiple indicators of SEP and Major Depressive Episode (MDE) among African Americans. METHODS: Data were drawn from the National Survey of American Life main interview and re-interview. MDE, at both 12 month and lifetime intervals, was assessed using the World Mental Health version of the Composite International Diagnostic Interview. Logistic regression models were adjusted for demographics. RESULTS: For 12-month MDE, household income and unemployment predicted greater odds of MDE among African American men, while there was an inverse relationship between education and 12-month MDE. Only unemployment was significantly associated with lifetime MDE among African American men. For African American women, a significant inverse relationship between household income and 12-month MDE was observed. CONCLUSIONS: Findings garnered from this study indicate that it is important to consider multiple measures of SEP in the prediction of depression among African Americans, and that the pattern of association between SEP and depression varies according to sex. Considering the paucity of studies that have explored the relationship between SEP and depression, additional research is needed to more firmly establish the relationship between SEP and depression. It is also important to consider stressors that may affect the relationship between SEP and depression among African Americans.

The associations between socio-economic status and major depressive disorder among Blacks, Latinos, Asians and non-Hispanic Whites: findings from the Collaborative Psychiatric Epidemiology Studies.

BACKGROUND: This study examined whether there were associations between individual measures of socio-economic status (SES) and the 12-month prevalence of major depressive disorder (MDD) in representative samples of Blacks, Latinos, Asians and Whites in the USA. METHOD: The data used were from the Collaborative Psychiatric Epidemiology Studies (CPES). RESULTS: There was an association between household income and MDD among Whites. However, the association was not statistically significant. Statistically significant associations were present between educational attainment and MDD among Whites. Among both Whites and Latinos, being out of the labor force was significantly associated with MDD. In analyses by nativity, being out of the labor force was significantly associated with MDD among US-born and foreign-born Latinos. CONCLUSIONS: Significant associations between various measures of SES and MDD were consistently observed among White and, in some cases, Latino populations. Future studies should continue to examine sociopsychological factors related to SES that increase the risk of MDD among people from racial-ethnic communities.

Magnetization transfer ratio abnormalities reflect clinically relevant grey matter damage in multiple sclerosis.

BACKGROUND: In multiple sclerosis, grey matter (GM) damage appears more clinically relevant than either white matter damage or lesion load. OBJECTIVE: We investigated if normal-appearing white matter (NAWM) and grey matter tissue changes assessed by magnetization transfer ratio were associated with long-term disability. METHODS: Sixty-nine people were assessed 20 years after presentation with a clinically isolated syndrome (CIS) [28 still CIS, 31 relapsing-remitting multiple sclerosis, 10 secondary progressive multiple sclerosis], along with 19 healthy subjects. Mean magnetization transfer ratio, peak height (PH) and peak location of the normalized magnetization transfer ratio histograms were determined in NAWM and grey matter, as well as, white matter and GM Fraction (GMF) and T(2)-weighted lesion load. RESULTS: Median expanded disability status scale for multiple sclerosis patients was 2.5 (range 1-8). GM-PH, and less so, NAWM mean and peak location, were lower in multiple sclerosis patients (P = 0.009) versus controls, relapsing-remitting multiple sclerosis versus CIS (P = 0.008) and secondary progressive multiple sclerosis versus relapsing-remitting multiple sclerosis (P = 0.002). GM-PH (as well as GMF) correlated with expanded disability status scale (r(s) = -0.49; P = 0.001) and multiple sclerosis functional score (r(s) = 0.51; P = 0.001). GM-PH independently predicted disability with similar strength to the associations of GMF with clinical measures. CONCLUSION: Grey matter damage was related to long-term disability in multiple sclerosis cohort with a relatively low median expanded disability status scale. Markers of intrinsic grey matter damage (magnetization transfer ratio) and tissue loss offer clinically relevant information in multiple sclerosis.

Upper dose thresholds for radiation-induced adaptive response against cancer in high-dose-exposed, cancer-prone, radiation-sensitive Trp53 heterozygous mice.

Trp53 heterozygous mice are radiation-sensitive and cancer-prone. Groups of 7-8-week-old female Trp53 heterozygous mice were exposed to 4 Gy of 60Co gamma radiation at high (0.5 Gy/min) or low (0.5 mGy/min) dose rate. Other groups received 10 or 100 mGy at low dose rate 24 h prior to the 4-Gy dose. Tumor frequency and latency were measured over the animals' life span. Exposure to 10 mGy prior to 4 Gy resulted in a small (approximately 5%) but significant life-span regain and increased latency (approximately 9%) for all malignant tumors taken together, but 100 mGy further reduced life span slightly (approximately 7%). Latency responses were tumor type-specific. The prior 10-mGy exposure resulted in a small (approximately 7%) regain in latency for lymphomas but no change in latency for spinal osteosarcomas. Increasing the adapting dose to 100 mGy eliminated the increase in lymphoma latency and further reduced life span (approximately 8%). A 10-mGy dose prior to 4 Gy at low dose rate had no effects. Adapting exposures had no significant effect on tumor frequency. We conclude that a single low dose induced a small protective response in vivo in Trp53+/- mice, reducing the carcinogenic effects of a subsequent large, high-dose-rate exposure by increasing tumor latency. The upper dose threshold at which low-dose protective effects gave way to detrimental effects was tumor type-specific, as found previously for spontaneous tumors in these same cancer-prone mice (Radiat. Res. 159, 320-327, 2003). However, the upper dose thresholds appear to be lower (below 100 mGy) for radiation-induced tumors than for the same tumors appearing spontaneously.

Low doses of radiation increase the latency of spontaneous lymphomas and spinal osteosarcomas in cancer-prone, radiation-sensitive Trp53 heterozygous mice.

Mice heterozygous for Trp53 are radiation-sensitive and cancer-prone, spontaneously developing a variety of cancer types. Osteosarcomas in the spine lead to paralysis, while lymphomas lead rapidly to death, distinct events that provide objective measures of latency. The effects of a single low-dose (10 or 100 mGy), low-dose-rate (0.5 mGy/min) (60)Co gamma irradiation on lymphoma or spinal osteosarcoma frequency and latency, defined as time of death or of onset of paralysis, respectively, were examined. Compared to spontaneous lymphomas or to spinal osteosarcomas leading to paralysis in unexposed mice, an exposure of 7-8-week-old Trp53(+/-) mice to 10 or 100 mGy had no significant effect on tumor frequency, indicating no effect on tumor initiation. All tumors are therefore assumed to be of spontaneous origin. However, a 10-mGy exposure reduced the risk of both lymphomas and spinal osteosarcomas by significantly increasing tumor latency, indicating that the main in vivo effect of a low-dose exposure is a reduction in the rate at which spontaneously initiated cells progress to malignancy. The effect of this adaptive response persisted for the entire life span of all the animals that developed these tumors. Exposure to 100 mGy delayed lymphoma latency longer than the 10-mGy exposure. However, the 100-mGy dose increased spinal osteosarcoma risk by decreasing overall latency compared to unexposed control mice. That result suggested that this higher dose was in a transition zone between reduced and increased risk, but that the dose at which the transition occurs varies with the tumor type.

Uranium and uranium decay series radionuclide dynamics in bone of rats following chronic uranium ore dust inhalation.

The accumulation and release of uranium and some uranium decay chain radionuclides were measured in the bones of rats that had been chronically exposed to inhaled uranium ore dust during the first half (approximately) of their natural adult lifespan. Endochondral bone (femur, tibia, humerus, radius, and ulna), membrane bone (skull roofing bones) and muscle of Sprague-Dawley rats (n = 55) that died at various times up to 65 weeks after the end of chronic inhalation of uranium ore dust aerosol (4.2 h d(-1) for 65 wk) and from age matched controls (n = 10), were analyzed for uranium, 230Th, 226Ra, 210Pb, and 210Po. Overall, during the period of dust inhalation, the nuclides accumulated in the above order of decreasing concentration in dry bone. However, the results demonstrate that there was some differential accumulation of uranium and uranium decay series radionuclides in muscle and two bone types of rats during the chronic inhalation period. The data also show that the bone levels of some, but not all, radionuclides decreased significantly with time after inhalation ceased. Lung uranium concentration at the time of death was a highly significant covariant for temporal changes in the levels of some radionuclides in both endochondral bone and membrane bone, indicating that lung remained a major source of these isotopes for accumulation in these bone types after ore dust inhalation had ceased. For some isotopes, the two bone types behaved differently during the dust inhalation period, and differently again after the dust inhalation ceased. The relative behavior of one bone type compared to the other for a particular isotope during the dust inhalation period did not predict the relative behavior after dust inhalation ceased. However, a faster accumulation of one bone type compared to the other for a particular isotope during the dust inhalation period predicted a faster decrease after dust inhalation ended.

Neighborhood disadvantage, stress, and drug use among adults.

This paper explores the relationships among neighborhood disadvantage, stress, and the likelihood of drug use in a sample of adults (N = 1,101). Using the 1995 Detroit Area Study in conjunction with tract-level data from the 1990 census, we find a positive relationship between neighborhood disadvantage and drug use, and this relationship remains statistically significant net of controls for individual-level socioeconomic status. Neighborhood disadvantage is moderately associated with drug related behaviors, indirectly through increased social stressors and higher levels of psychological distress among residents of disadvantaged neighborhoods. A residual effect of neighborhood disadvantage remains, net of a large number of socially relevant controls. Finally, results from interactive models suggest that the relationship between neighborhood disadvantage and drug use is most pronounced among individuals with lower incomes.

Health system costs of metastatic breast cancer.

To assess the costs of treating patients with incurable breast cancer, all health system costs during the interval from diagnosis of first recurrence or metastasis until death for 75 female subjects randomly selected from those known to have died of breast cancer in British Columbia, Canada between July 1, 1995 and December 31, 1996, were identified. Costs were determined from several databases within the British Columbia (BC) Ministry of Health, as well as from BC Cancer Agency patient charts. The mean total cost to the health system was CDN $36,474.33 (95% confidence interval $29,752-$43,196) per subject. The mean costs were highest for the youngest age group and lowest for the middle age group, but these only differed by $2,300. Inpatient costs accounted for the greatest proportion of the total, over 50% in all age groups. This data may be valuable in assessing the cost-effectiveness of interventions that are known to affect mortality due to breast cancer.

Diagnosis of metachronous contralateral breast cancer.

The purpose of this study was to compare the characteristics of primary breast cancers (PBCs) and metachronous contralateral breast cancers (MCBCs). Between 1984 and 1996, 236 women treated with curative intent for PBC who developed a MCBC >6 months after initial diagnosis (without previous evidence of distant metastases) were retrospectively evaluated for clinical and pathologic characteristics and method of diagnosis of their tumors. There were more noninvasive cancers among the MCBCs than the PBCs (11.4% and 5.1%, respectively, p < 0.02). Among the invasive cancers, the mean size of the MCBCs was smaller than the PBCs (1.94 versus 2.55 cm, p < 0.001). MCBCs were more likely than PBCs to be mammographically detected (46.2% versus 19.9%, p < 0.001). Tumor size was correlated with the method of diagnosis. The mean tumor size was 1.39, 2.02, and 2.69 cm for mammogram-, physician-, and patient-detected tumors, respectively. Among patients having axillary lymph node dissections, mammogram- and physician-detected tumors were less likely to have lymph node metastases than patient-detected tumors (22.0% versus 41.2%, p < 0.005). Regular follow-up of breast cancer patients diagnoses MCBCs when they are smaller and less likely to have nodal metastases than PBCs mainly because of early mammographic detection.

Race/ethnicity and the 2000 census: recommendations for African American and other black populations in the United States.

This commentary considers the implications of the assessment of racial/ethnic status for monitoring the health of African Americans and other Black populations in the United States. It argues that because racial disparities in health and other social indicators persist undiminished, the continued assessment of race is essential. However, efforts must be made to ensure that racial data are of the highest quality. This will require uniform assessment of racial status that includes identifiers for subgroups of the Black population. Research also indicates that the health of multiracial persons varies by maternal race. Thus, efforts to monitor multiracial status should assess the race of both parents. More attention should also be given to analysis and interpretation of racial data and to the collection of additional data that capture characteristics linked to race (such as socioeconomic factors and racism) that may adversely affect health.

The contribution of hope to the quality of life among aging African Americans: 1980-1992.

This study examined age differences between 1979-80 and 1992 in the quality of life of African Americans using panel data from the National Survey of Black Americans. Of particular interest was the role of the hope dimension of personal efficacy in accounting for variance in general well-being, beyond that contributed by social demographic and economic indicators. Hierarchical regression analyses revealed that hope and family satisfaction in 1980 consistently accounted for significant amounts of variance in general life satisfaction in the 1992 fourth wave of data among all three cohorts. For older respondents, increased frequency of contact with friends and family help were the most important contributors to high satisfaction. Across waves in all age cohorts family satisfaction and contact with friends were most important in contributing to life satisfaction. Implications for further research on well-being among African Americans were discussed.

A decision analysis of the effect of avoiding axillary lymph node dissection in low risk women with invasive breast carcinoma.

BACKGROUND: Evidence that avoiding axillary lymph node dissection (AxD) strikes an appropriate balance between morbidity and recurrence risk in patients with invasive breast carcinoma generally is anecdotal and without a formally quantified basis. The current study presents a decision analysis of the difference in 5-year disease free survival (DFS) rate between treatment scenarios with and without routine AxD. METHODS: To derive quantitative estimates of the effect of avoiding AxD on 5-year DFS, the authors examined outcomes for women undergoing 2 treatment scenarios: AxD or no AxD with adjuvant therapy decisions based on risk factors in the primary tumor. Eligible patients belonged to 2 lymph node metastases risk groups: low (patients without palpable lymph nodes and lymphatic or vascular invasion [LVI] negative tumors < or = 0.5 cm in greatest dimension) and moderate (patients with mammographically detected, LVI negative tumors, between 0.6-2.0 cm in greatest dimension or patients with palpable LVI negative tumors between 0.6-1.0 cm in greatest dimension with nonpalpable lymph nodes). Along with observed data regarding treatment and recurrence, the authors employed estimates of the efficacy of chemotherapy, tamoxifen, and regional radiation therapy derived from published randomized trials to estimate the 5-year DFS rate for treatment scenarios with and without AxD. RESULTS: Patients in the low risk group had a 5% risk of lymph node metastases. In these women, eliminating AxD and treating no patients with chemotherapy and/or tamoxifen resulted in a < 1% decrease in the 5-year DFS rate. Patients in the moderate risk group had a 10% risk of lymph node metastases. Eliminating AxD and treating only those women with Grade 3 tumors > 1 cm in greatest dimension with chemotherapy and/or tamoxifen resulted in a 1.8% decrease in the 5-year DFS rate. However, if all patients in this group were treated with chemotherapy and/or tamoxifen and no AxD, the 5-year DFS rate increased by 2.7%. CONCLUSIONS: In patients with a low risk of lymph node metastases, it was estimated that eliminating AxD may result in only minimal changes in the estimated 5-year DFS rate.

Effect of time interval between breast-conserving surgery and radiation therapy on ipsilateral breast recurrence.

PURPOSE: To examine the effect of the time interval (interval) between breast-conserving surgery (BCS) and the start of radiation therapy (RT) on the subsequent risk of ipsilateral breast cancer recurrence (IBR). METHODS AND MATERIALS: We reviewed interval and a number of prognostic and treatment factors among 1,962 women treated with BCS and RT for invasive breast cancer diagnosed between January 1, 1989 and December 31, 1993 in British Columbia, Canada. Subjects were female, less than 90 years old at diagnosis, not treated with chemotherapy, not stage T4 or M1, and had survived more than 30 days from diagnosis. The cumulative incidence of IBR was estimated in four interval groups: 0-5, 6-8, 9-12, and 13+ weeks. Only 23 women had an interval of greater than 20 weeks between BCS and start of RT. To assess whether an imbalance of prognostic and treatment factors could be obscuring real differences between the interval groups, Cox proportional hazards regression analyses were conducted. RESULTS: Median follow-up was 71 months. The crude incidence of IBR for the entire sample was 3.9%. The cumulative incidence of IBR in the 6-8, 9-12, and 13+ week groups was not statistically significantly different from the cumulative incidence of IBR in the 0-5 week group. Multivariate analyses demonstrated that patients not using tamoxifen p = 0.027) and those with grade 3 histology (p = 0.003) were more likely to recur in the breast. Interval between BCS and RT was not a statistically significant predictor of breast recurrence when entered into a model incorporating tamoxifen use and tumor grade (0-5 vs. 6-8 weeks, p = 0.872; 0-5 vs. 9-12 weeks, p = 0.665; 0-5 vs. 13+ weeks, p = 0.573). CONCLUSIONS: We found no univariate or multivariate difference in ipsilateral breast cancer recurrence between intervals of 0 to 20 weeks from breast conserving surgery to start of radiation therapy, in a population-based, low risk group of women not receiving adjuvant chemotherapy, after controlling for other factors important in predicting ipsilateral breast cancer recurrence.

The adaptive response modifies latency for radiation-induced myeloid leukemia in CBA/H mice.

We have investigated the effect of the adaptive response on acute myeloid leukemia (AML) induced in CBA/Harwell mice by a chronic radiation exposure. Groups of mice irradiated with a total dose of 1. 0 Gy at two different chronic dose rates (0.5, 0.004 Gy/h) had similar frequencies of AML. Compared to control animals that did not develop AML, irradiation at either of these dose rates did not change the longevity of the mice that did not die of leukemia. The survival rates of irradiated mice that did develop leukemia in the two groups were not different from each other, indicating that the dose rates produced similar responses and therefore were both chronic exposures. We then tested the ability of a chronic 10-cGy (0. 5 Gy/h) exposure to ionizing radiation, mild hyperthermia (40.5 degrees C whole-body, 60 min) or treatment with interleukin-1 (1500 U i.p.) to induce an adaptive response and modify the frequency or latency of AML which resulted from a subsequent (24 h later) 1.0-Gy (0.5 Gy/h) chronic radiation exposure. The frequency of radiation-induced leukemia was not changed in mice given any of the three adapting treatments 24 h prior to the chronic 1.0-Gy dose that induced leukemia. However, the latent period for development of AML was significantly increased by both the prior low radiation dose and mild hyperthermia treatment. Injection of interleukin-1, in contrast, may have reduced the latent period. Similar to the single 1.0-Gy chronic exposure alone, none of the adapting treatments prior to that exposure influenced the survival of animals that did not develop AML. These results indicate that an earlier exposure to a small adapting dose of radiation or to a mild heat stress can influence secondary steps in radiation-induced carcinogenesis.