Using zebrafish to assess the effect of chronic, early developmental exposure to environmentally relevant concentrations of 5-fluorouracil and leucovorin.

Environmental contaminants can deleteriously affect aquatic animals. One such contaminant is 5-fluorouracil (5-FU), a long-prescribed chemotherapeutic drug. Leucovorin (LV) is co-administered with 5-FU, potentiating its effects. Zebrafish (Danio rerio) larvae were reared in ng/L treatments of either 5-FU, LV, or a combined 5-FU/LV mixture for 8 dy. Survival was measured daily and swimming behavior assessed every other day. After 8 dy, larval length was measured, and densitometry of p53-labeled cryostat sections determined the extent of apoptosis. No significant differences in survival or apoptosis were found; larvae in the highest concentrations were largest. Changes in behavior of 5-FU-treated larvae were based on exposure duration; changes in LV-treated larvae were affected by drug concentration and duration. Larvae co-exposed to 5-FU/LV had responses like 5-FU-treated larvae. Overall, early developmental exposure of zebrafish larvae to environmentally-relevant concentrations of 5-FU and LV did not adversely affect survival, growth, and behavior suggesting realistic concentrations are sublethal and non-toxic.

Foodborne and waterborne illness among Canadian Indigenous populations: A scoping review.

BACKGROUND: Indigenous populations are often at higher risk for foodborne illness than the general Canadian population. OBJECTIVE: To investigate the extent of the literature on the link between food safety and the occurrence of foodborne and waterborne illness in Canadian Indigenous populations. METHODS: A scoping review was conducted using search strings in five databases and grey literature to identify all papers that studied a Canadian Indigenous population and referred to any potential associations between food safety (including consumption and preparation of traditional foods and retail foods) or water safety practices and food or waterborne illness. Two authors screened papers based on inclusion and exclusion criteria. Included documents were analyzed for emergent themes. RESULTS: From 1,718 unique records identified, 21 documents were selected. Foodborne illness was most common in children up to 14 years old. Walrus, seal, caribou and whale were the most common traditional foods tied to foodborne illness and were primarily associated with botulism and trichinosis. Aside from consuming the food raw, fermentation was the most common traditional preparation method linked to foodborne illness. There was concern about the safety of retail food but no clear link was identified with foodborne illness. Lastly, although there was concern about tap water, the use of alternate water sources, such as untreated brook water, and hygiene and cleaning practices in communities with boil water advisories were the most common risk behaviours associated with waterborne illness. CONCLUSION: Consumption of certain game meats, as well as the use of traditional fermentation practices may lead to an increased risk of foodborne illness among Indigenous populations. Concern about tap water may lead to use of unsafe alternate water sources. Further research is needed to examine potential culturally appropriate food and water safety opportunities.

Synthesis, characterization, and water oxidation by a molecular chromophore-catalyst assembly prepared by atomic layer deposition. The "mummy" strategy.

A new strategy for preparing spatially-controlled, multi-component films consisting of molecular light absorbing chromophores and water oxidation catalysts on high surface area, mesoporous metal oxide surfaces is described. Atomic layer deposition (ALD) is used to embed a surface-bound chromophore in a thin layer of inert Al2O3, followed by catalyst binding to the new oxide surface. In a final step, catalyst surface-binding is stabilized by a subsequent ALD overlayer of Al2O3. The ALD assembly procedure bypasses synthetic difficulties arising from the preparation of phosphonic acid derivatized, covalently-linked assemblies. An ALD mummy-based assembly has been used to demonstrate photoelectrochemical dehydrogenation of hydroquinone. Electrocatalytic water oxidation at pH 8.8 is observed over a 2 hour electrolysis period and light-assisted water oxidation over a 6 hour photolysis period with O2 detected with a generator-collector electrode configuration.

The diets of school-aged Aboriginal youths in Canada: a systematic review of the literature.

BACKGROUND: Most national surveys examining diet leave large segments of the Aboriginal population under-represented. The present study aimed to: (i) review primary research studies that investigated the dietary intakes of Canadian school-aged Aboriginal youths; (ii) summarise the tools and methodologies currently used to measure diet in this population; and (iii) identify knowledge gaps and suggest areas of future research. METHODS: A systematic review of research published between January 2004 and January 2014 related to the diets of Canadian school-aged (6-18 years) Aboriginal youths was undertaken, including Medline, Scopus, ERIC, Web of Science and Google Scholar databases. Studies were summarised based on purpose, year, sample population, setting, dietary assessment method and main findings. RESULTS: Twenty-four studies were reviewed, all of which were cross-sectional in design. Most (n = 16; 67%) were from Ontario or Quebec, investigated the diets of First Nations (n = 21; 88%) youths and took place in remote or isolated settings (n = 18; 75%). Almost all of the studies used the 24-h recall to assess intake (n = 19; 79%), of which 89% used a single recall. The findings suggest that the diets of Aboriginal youths could be improved. Of particular concern are inadequate intakes of vegetables and fruit, milk and alternatives, fibre, folate, vitamin A, vitamin C, calcium and vitamin D, concomitant with an excess consumption of sugar sweetened beverages, snacks and fast foods. Traditional foods remain important but tend to be consumed infrequently. CONCLUSIONS: The diets of Canadian Aboriginal youths are energy-dense and nutrient-poor. The diets of Inuit and Métis youths, in particular, and perceptions of a balanced diet warrant further investigation.

Implementation of a community greenhouse in a remote, sub-Arctic First Nations community in Ontario, Canada: a descriptive case study.

INTRODUCTION: Food insecurity is prevalent in northern communities in Canada and there is a movement to improve food security through both the re-vitalization of traditional harvesting practices as well as through sustainable agriculture initiatives. Gardening in northern communities can be difficult and may be aided by a community greenhouse. The objective of this project was to conduct a descriptive case study of the context and process surrounding the implementation of a community greenhouse in a remote, sub-Arctic First Nations community in Ontario, Canada. METHOD: Data sources included semi-directed interviews with a purposive and snowball sample of key informants (n=14), direct observations (n=32 days), written documentation (n=107), and photo-documentation (n=621 total). Digital photographs were taken by both a university investigator during community visits and a community investigator throughout the entire project. The case study was carried out over 33 months; from early 2009 until October of 2011. Thematic data analyses were conducted and followed a categorical aggregation approach. RESULTS: Categories emerging from the data were appointed gardening-related themes: seasons, fertile ground, sustainability, gardeners, ownership, participant growth, and sunshine. Local champions were critical to project success. Uncertainty was expressed by several participants regarding ownership of the greenhouse; the local community members who championed the project had to emphasize, repeatedly, that it was community owned. Positive outcomes included the involvement of many community members, a host of related activities, and that the greenhouse has been a learning opportunity to gain knowledge about growing plants in a northern greenhouse setting. A strength of the project was that many children participated in greenhouse activities. CONCLUSIONS: Community and school greenhouse projects require local champions to be successful. It is important to establish guidelines around ownership of a greenhouse and suitable procedures for making the building accessible to everyone without compromising security. Implementing a greenhouse project can engage community members, including children, and provide a great learning opportunity for gardeners in a remote, northern community.

Study of psychrophilic and psychrotolerant micro-organisms isolated in cold rooms used for pharmaceutical processing.

AIMS: To examine for psychrophilic or psychrotolerant micro-organisms in pharmaceutical cold rooms (in relation to numbers, incidents and species) and to determine, where such micro-organisms are present, whether standard microbiological environmental monitoring regimes require modification. This is presented as a case study. METHODS AND RESULTS: Comparative environmental monitoring within different pharmaceutical facility cold rooms (using standard mesophilic and low temperature incubation). Data were collected over two periods, 5 years apart. The results indicated that psychrophilic micro-organisms were not present and that those micro-organisms deemed psychrotolerant, primarily pseudomonads, could be grown on standard media under mesophilic conditions. CONCLUSIONS: Psychrophilic micro-organisms were not detected and those considered to be psychrotolerant were only found in low numbers. Pyschrotolerant organisms were recovered under both low temperature incubation conditions and under standard conditions (between 20 and 35°C). Further evaluation may be required, using alternative agar, and microbiologists should regularly review the species recovered to note differences between different environments. SIGNIFICANCE AND IMPACT OF THE STUDY: The study came about from requests made by US and UK regulators concerning the risk of any extremophiles present in pharmaceutical manufacturing facilities upon product safety. Regulators expressed concerns about whether standard, and accepted, environmental monitoring regimes were capable of detecting such micro-organisms. The data provide a benchmark to support pharmaceutical manufacturers in relation to their existing monitoring programmes or as a case study with which to undertake a similar study.

Loss of tumor progression locus 2 (tpl2) enhances tumorigenesis and inflammation in two-stage skin carcinogenesis.

Tumor progression locus 2 (Tpl2) is a serine/threonine kinase in the mitogen-activated protein kinase signal transduction cascade known to regulate inflammatory pathways. Previously identified as an oncogene, its mutation or overexpression is reported in a variety of human cancers. To address its role in skin carcinogenesis, Tpl2(-/-) or wild-type (WT) C57BL/6 mice were subjected to a two-stage dimethylbenzanthracene/12-O-tetradecanoylphorbol-13-acetate (TPA) mouse skin carcinogenesis model. Tpl2(-/-) mice developed a significantly higher incidence of tumors (80%) than WT mice (17%), as well as a reduced tumor latency and a significantly higher number of total tumors (113 vs 6). Moreover, Tpl2(-/-) mice treated with TPA experienced significantly higher nuclear factor kappaB (NF-κB) activation, edema, infiltrating neutrophils and production of proinflammatory cytokines than did WT mice. We investigated the role of the p38, JNK, MEK and NF-κB signaling pathways both in vitro and in vivo in WT and Tpl2(-/-) mice by using inhibitors for each of these pathways. We confirmed that the proinflammatory effect in Tpl2(-/-) mice was due to heightened activity of the NF-κB pathway. These studies indicate that Tpl2 may serve more as a tumor suppressor than as an oncogene in chemically induced skin carcinogenesis, with its absence contributing to both tumorigenesis and inflammation.

Capillary pressure may predict preclinical changes in the eye.

AIMS/HYPOTHESIS: Microvascular dysfunction is associated with end-organ damage. Macular oedema is an important component of diabetic retinopathy. Macular thickness can be accurately quantified by optical coherence tomography (OCT), enabling accurate assessment of the macular prior to clinically apparent abnormalities. We investigated whether macular (fovea) thickness in non-diabetic individuals is related to the microvascular variables controlling fluid filtration across a blood vessel wall, in particular capillary pressure and the microvascular filtration capacity (Kf). METHODS: We recruited 50 non-diabetic individuals (25 men, 25 women; age range: 26-78 years; BMI range: 20-46 kg/m(2)). Fovea thickness was assessed by OCT. Microvascular assessments included: finger nailfold capillary pressure; Kf; microvascular structural assessments, i.e. skin vasodilatory capacity, minimum vascular resistance (MVR) and microvascular distensibility; and endothelial function. RESULTS: At 214.6 (19.9) microm (mean [SD]), fovea thickness was within normal range. Capillary pressure, adjusted for BMI, was associated with fovea thickness (standardised beta 0.573, p = 0.006, linear regression). Fovea thickness was not associated with Kf, microvascular structural assessments or endothelial function. Capillary pressure was still associated with fovea thickness when adjusted for microvascular variables (Kf, vasodilatory capacity, MVR, microvascular distensibility or endothelial function), or for risk factors for diabetes (systemic blood pressure, insulin sensitivity, inflammation, glycaemic status and lipids) and age. CONCLUSIONS/INTERPRETATION: Capillary pressure, a key determinant of movement of fluid across a blood vessel wall, is associated with fovea thickness in non-diabetic individuals. This suggests that with regard to potential preventative or therapeutic targets, attention should be directed at the mechanisms determining retinal microvascular pressure.

Adiposity is a major determinant of plasma levels of the novel vasodilator hydrogen sulphide.

AIMS/HYPOTHESIS: Hydrogen sulphide is a recently identified endogenous endothelium-dependent vasodilator. Animal models of diabetes have shown that low plasma H(2)S levels are associated with marked endothelial dysfunction and insulin resistance. However, human studies on H(2)S and vascular function in health and disease are lacking. METHODS: Plasma was obtained from male patients with type 2 diabetes (n = 11), overweight (n = 16) and lean (n = 11) volunteers. H(2)S levels were determined by zinc trap spectrophotometry. Anthropometric measurements (BMI/waist:hip ratio), lipid profile, systemic blood pressure, biochemical indices of diabetes (fasting glucose, insulin sensitivity, Hb(1Ac)) and microvascular function (minimum vascular resistance) were determined. RESULTS: Median plasma H(2)S levels (25th, 75th percentiles) in age-matched lean, overweight and type 2 diabetes individuals were 38.9 (29.7, 45.1) micromol/l, 22.0 (18.6, 26.7) micromol/l and 10.5 (4.8, 22.0) micromol/l, respectively. Median plasma H(2)S levels were significantly lower in patients with type 2 diabetes compared with lean (p = 0.001, Mann-Whitney) and overweight participants (p = 0.008). Median plasma H(2)S levels in overweight participants were significantly lower than in lean controls (p = 0.003). Waist circumference was an independent predictor of plasma H(2)S (R (2) = 0.423, standardised beta: -0.650, p < 0.001). This relationship was independent of diabetes, which only contributed a further 5% to the model (R (2) = 0.477). Waist circumference or other measures of adiposity (waist:hip ratio/BMI) remained independent predictors of plasma H(2)S after adjustment for systolic blood pressure, microvascular function, insulin sensitivity, glycaemic control and lipid profile. CONCLUSIONS/INTERPRETATION: Plasma H(2)S levels are reduced in overweight participants and patients with type 2 diabetes. Increasing adiposity is a major determinant of plasma H(2)S levels.

Efficacy of electrotactile vestibular substitution in patients with peripheral and central vestibular loss.

Vestibular dysfunction of either central or peripheral origin can significantly affect balance, posture, and gait. We conducted a pilot study to test the effectiveness of training with the BrainPort balance device in subjects with a balance dysfunction due to peripheral or central vestibular loss. The BrainPort balance device transmits information about the patient's head position via electrotactile stimulation of the tongue. Head position data is sensed by an accelerometer and displayed on the tongue as a pattern of stimulation. This pattern of stimulation moves forward, backward, and laterally on the tongue in direct response to head movements. Users of the device were trained to use this stimulation to adjust their position in order to maintain their balance. Twenty-eight subjects with peripheral or central vestibular loss were trained with the BrainPort balance device and tested using the following standardized quantitative measurements of the treatment effects: Computerized Dynamic Posturography (CDP) using the Sensory Organization Test (SOT), Dynamic Gait Index (DGI), Activities-specific Balance Confidence Scale (ABC), and Dizziness Handicap Inventory (DHI). All subjects had chronic balance problems and all but one had previously participated in vestibular rehabilitation therapy. The scores on the clinical tests upon entry into the study were compared to their scores following training with the BrainPort balance device. Our results exhibit consistent positive and statistically significant improvements in balance, posture and gait. These results exceed what could normally be achieved in three to five days of traditional balance training alone. Since this was not a controlled study, we are unable to distinguish the degree to which these improvements are attributable to training with the BrainPort balance device versus the balance exercises performed by all subjects as a part of the BrainPort training sessions. Nonetheless, after training with the BrainPort balance device, all subjects demonstrated significant improvements in performance beyond what might be expected from conventional vestibular rehabilitation therapy.

Efficacy of electrotactile vestibular substitution in patients with bilateral vestibular and central balance loss.

Patients with bilateral vestibular loss (BVL) of both central and peripheral origin experience multiple problems with balance and posture control, movement, and abnormal gait.Wicab, Inc. has developed the BrainPort balance device to transmit head position/orientation information normally provided by the vestibular system to the brain through a substitute sensory channel: electrotactile stimulation of the tongue. Head-orientation data (artificially sensed) serves as the input signal for the BrainPort balance device to control the movement of a small pattern of stimulation on the tongue that relates to head position in real-time. With training, the brain learns to appropriately interpret the information from the device and utilize it to function as it would with data from a normal-functioning natural sense. Ina total of 40 subjects trained with the BrainPort, 18 have been tested using standardized quantitative measurements of the treatment effects. A specialized set of exercises, testing, and training procedures has been developed that may serve as the course of intensive physical therapy with the BrainPort balance device. Our results demonstrate consistent positive and statistically significant balance rehabilitation effects independent of aging and etiology of balance deficit.

Palpable breast cancers are inherently different from nonpalpable breast cancers.

BACKGROUND: We examined the clinicopathologic profile of T1 cancers to determine whether palpable cancers are different from nonpalpable cancers. METHODS: A prospective database was reviewed. Palpable T1 cancers were compared with nonpalpable T1 cancers. Initial significance was determined by chi2 analysis. Factors found to be significant were then reanalyzed. controlling for tumor size by logistic or linear regression, as appropriate. RESULTS: Of 1263 T1 cancers treated between 1981 and 2000, 857 (68%) were palpable and 401 (32%) were nonpalpable. Palpability correlated with pathologic tumor size, mitotic grade, nuclear grade, high S-phase, lymphovascular invasion, nodal positivity, and lack of extensive intraductal component, multifocality, and multicentricity. There was no significant difference in estrogen receptor, progesterone receptor or Her-2/neu status, ploidy, or DNA index. Breast cancer-specific survival was worse for patients with palpable cancers. CONCLUSIONS: Palpable cancers are inherently different from nonpalpable cancers, with a less diffuse growth pattern, higher metastatic potential, higher proliferative activity, more nuclear abnormalities, and a worse prognosis.

Religion and mental health among women veterans with sexual assault experience.

OBJECTIVE: Religion has been shown to have a positive impact on well-being and to play an important role in coping with stressful life events. However, the buffering effect of religiosity on mental health, after a particularly stressful life event such as sexual assault, has not been studied. In this study we examined the buffering effect of religion on mental health and depression for women who report experiencing sexual assault while in the military. METHOD: The sample includes a nationally representative sample of 3,543 women veterans who use VA ambulatory care. Two dimensions of religiosity were used: organizational (frequency of religious service attendance) and subjective (the extent religious beliefs are a source of strength/comfort). Mental health was measured by the mental component summary (MCS) from the SF36 and depressive symptoms were measured by the Center for Epidemiologic Studies-Depression (CES-D) scale. RESULTS: Women veterans who reported experiencing sexual assault while in the military had lower mental health scores and higher levels of depression. Linear regression analysis indicated that these negative impacts diminished with increased frequency of religious service attendance, supporting the buffering effect of organizational religiosity on mental health and depression. Although the buffering effect of subjective religiosity was not evident, subjective religiosity was shown to be positively associated with better mental health in both groups of women with and without sexual assault experience in the military. CONCLUSIONS: Frequent religious service attendance buffers the negative impacts of sexual assault on mental health and depression of women veterans. The potential of integrating religiosity in designing interventions is discussed.

Improvements in circulating cholesterol, antioxidants, and homocysteine after dietary intervention in an Australian Aboriginal community.

BACKGROUND: Poor nutrition contributes to high rates of coronary heart disease among Australian Aboriginal populations. Since late 1993, the Aboriginal community described here has operated a healthy lifestyle program aimed at reducing the risk of chronic disease. OBJECTIVE: We evaluated the effectiveness of a community-directed intervention program to reduce coronary heart disease risk through dietary modification. DESIGN: Intervention processes included store management policy changes, health promotion activities, and nutrition education aimed at high-risk individuals. Dietary advice was focused on decreasing saturated fat and sugar intake and increasing fruit and vegetable intake. Evaluation of the program included conducting sequential, cross-sectional risk factor surveys at 2-y intervals; measuring fasting cholesterol, lipid-soluble antioxidants, and homocysteine concentrations; and assessing smoking status. Nutrient intakes were estimated from analysis of food turnover in the single community store. RESULTS: There was a significant reduction in the prevalence of hypercholesterolemia (age-adjusted prevalences were 31%, 21%, and 15% at baseline, 2 y, and 4 y, respectively; P < 0.001). There were significant increases in plasma concentrations of alpha-tocopherol, lutein and zeaxanthin, cryptoxanthin, and beta-carotene across the population. Retinol and lycopene concentrations did not change significantly. Mean plasma homocysteine concentrations decreased by 3 micromol/L. There was no significant change in smoking prevalence between the 2 follow-up surveys. There was an increase in the density of fresh fruit and vegetables and carotenoids in the food supply at the community store. CONCLUSION: This community-directed dietary intervention program reduced the prevalence of coronary heart disease risk factors related to diet.

Health status assessments using the Veterans SF-12 and SF-36: methods for evaluating otucomes in the Veterans Health Administration.

This article describes a study in which the administration of two health surveys, the Veterans SF-36 and SF-12, by telephone and mail-out was used to assess the differences in the health surveys' costs and scores by mode of administration and determine which mode was cost-efficient. The study employed a crossover design: after 12 unsuccessful attempts to contact patients by telephone, the patients were administered the survey by mail, and after 2 unsuccessful mail-outs, up to three attempts were made to interview the patients by telephone. The analysis of the data showed that mail administration, with or without crossover to telephone, was more cost-efficient than telephone administration, having both lower average total and variable costs per completed questionnaire. Overall, telephone administration was about 30% more expensive that mail administration, primarily due to the cost of labor. The marginal cost of an additional completed Veterans SF-12 or Veterans SF-36 was also substantially lower for mail administration. Mail administration without crossover to telephone administration was the most cost-efficient strategy for administering both the Veterans SF-12 and SF-36. The results of this study strongly suggest the need to consider the mode of administration if questionnaires like the Veterans SF-12 or SF-36 are to be used to assess health outcomes within and across large health care systems.

Knee effusions, popliteal cysts, and synovial thickening: association with knee pain in osteoarthritis.

OBJECTIVE: To evaluate the association of effusions, popliteal cysts, and synovial thickening with knee symptoms in older persons with and without radiographic (XR) osteoarthritis (OA), using magnetic resonance imaging (MRI). METHODS: Subjects with and without knee symptoms were recruited from Veterans Affairs and community sources. All had weight-bearing knee radiographs. Subjects were divided into 3 groups: Knee pain/XROA group had knee symptoms and radiographic OA; No knee pain/XROA group had no knee symptoms and radiographic OA; and No knee pain/no XROA group had no knee symptoms and a normal radiograph. A single knee was imaged using a 1.5 T MR scanner using T1 and T2 weighted and proton density SE imaging sequences. MRI were read for effusion, popliteal cysts, and synovial thickening. RESULTS: The mean age of subjects was 67.0 years (66.6% male). We studied 381 subjects with Knee pain/XROA, 52 with No knee pain/XROA, and 25 with No knee pain/no XROA. The prevalence of moderate or larger effusions was: Knee pain/XROA 54.6%, No knee pain/XROA 15.6%, and No knee pain/no XROA 11.1%. Popliteal cysts were present in 33.0% of Knee pain/XROA subjects, 28.0% No knee pain/XROA, and 9.1% No knee pain/no XROA. After adjusting for the severity of radiographic OA, there was a difference between those with and without knee pain in prevalence of moderate or larger effusions (p < 0.001) and synovial thickening, independent of effusion (p < 0.001), but not in the prevalence of popliteal cysts. Further, among those in Knee pain/OA group, synovial thickening was associated with the severity of knee pain. CONCLUSION: Effusions and popliteal cysts are common in middle aged and elderly people. After adjusting for the degree of radiographic OA, moderate or large effusions and synovial thickening were more frequent among those with knee pain than those without pain, suggesting these features are associated with the pain of knee OA. In those with knee symptoms, synovial thickening is uniquely associated with the severity of knee pain.

Racial differences in the use of lumbar spine radiographs: results from the Veterans Health Study.

STUDY DESIGN: We analyzed data from the Veterans Health Study, a longitudinal study of male patients receiving VA ambulatory care. OBJECTIVE: To determine whether clinical differences and/or race account for disparities between white and nonwhite patients in the use of lumbar spine radiographs. SUMMARY AND BACKGROUND DATA: Four hundred one patients with low back pain (LBP) receiving ambulatory care services in four VA outpatient clinics in the greater Boston area were followed for 12 months. METHODS: Participants were mailed the Medical Outcome Study Short Form Health Survey (SF-36) and had scheduled interviews that included the completion of a low back questionnaire, a comorbidity index, and a straight leg raising (SLR) test. Using self-reported racial data, patients were grouped as whites (315 patients) and nonwhites (among whom 22 were black, 4 nonwhite Hispanics, and 1 other race). RESULTS: Nonwhite patients had lumbar spine films more often (13 of 27, 48%) than white patients (87 of 315, 27%)(P = 0.02). Nonwhite patients had higher pain intensity scores than white patients (63 +/- 21 vs. 48 +/- 21, P < 0.01) and were more likely to have radiating leg pain (20 of 27, 76%; compared with 171 of 315, 55%; P = 0.01) than white patients. Nonwhite patients had worse physical functioning (P = 0.01), general health perception (P = 0.05), social functioning (P = 0.02), and role limitations because of emotional problems (P < 0.01). At higher LBP intensity level, nonwhite patients received more lumbar spine films (20 of 27, 74%) than did white patients (155 of 315, 50%)(P < 0.01). Among patients with positive SLR test, nonwhite patients also had lumbar spine films more often (5 of 22, 23%) than white patients (29 of 315, 11%) (P < 0.01). However, after adjusting for multiple clinical characteristics, race was no longer found to be an independent predictor of lumbar spine radiograph use. A positive SLR test remained to be associated with higher radiograph use, whereas better mental health status was associated with lower radiograph use. CONCLUSIONS: There was greater use of lumbar spine radiographs by nonwhite patients compared with white patients. This remained true when patients were subcategorized by severity of LBP or SLR test. However, race had no influence when multiple clinical characteristics of the patients were controlled for simultaneously. This study demonstrates the importance of careful and comprehensive case-mix adjustment when assessing apparent differences in the use of medical services.

The management of ductal carcinoma in situ of the breast.

Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous group of lesions with diverse malignant potential. It is the most rapidly growing subgroup within the breast cancer family with more than 42 000 new cases diagnosed in the United States during 2000. Most new cases are nonpalpable and are discovered mammographically. Treatment is controversial and ranges from excision only, to excision with radiation therapy, to mastectomy. Prospective randomized trials reveal an approximate 50% reduction in local recurrence rate overall with the addition of radiation therapy to excisional surgery, but the published prospective data do not allow the selection of subgroups in whom the benefit from radiation therapy is so small that its risks outweigh its benefits. Nonrandomized single facility series suggest that age, family history, nuclear grade, comedo-type necrosis, tumor size and margin width are all important factors in predicting local recurrence and that one or more of these factors could be used to select subgroups of patients who do not benefit sufficiently from radiation therapy to merit its use. When all patients with ductal carcinoma in situ are considered, the overall mortality from breast cancer is extremely low, only about 1-2%. When conservative treatment fails, approximately 50% of all local recurrences are invasive breast cancer. In spite of this, the mortality rate following invasive local recurrence is relatively low, about 12% with eight years of actuarial follow-up. Genetic changes routinely precede morphological evidence of malignant transformation. Lessons learned from ongoing basic science research will help us to identify those DCIS lesions that are unlikely to progress and to prevent progression in the rest.

Predicting axillary nodal positivity in 2282 patients with breast carcinoma.

Axillary lymph node status continues to be the single most important prognostic variable for breast cancer survival despite significant progress in the molecular and genetic characterization of breast malignancies. All patients with invasive breast cancer who underwent axillary lymph node dissection as part of their treatment were evaluated by 11 clinical and pathologic factors, including the primary lesion's T category (TNM staging system), whether the lesion was clinically palpable, the presence of lymphatic or vascular invasion, nuclear grade, estrogen and progesterone receptors, S-phase, age, HER2/neu overexpression, histology (infiltrating lobular or ductal), and ploidy. A total of 2282 axillary dissections were performed: 391 in patients with ductal carcinoma in situ (DCIS) [3 of which (0.8%) contained metastases] and 1891 in patients with invasive breast cancer [680 of which (36%) contained metastases]. Multivariate analysis of patients with invasive cancer identified four factors as independent predictors of axillary lymph node metastases: lymph/vascular invasion, tumor size, nuclear grade, tumor palpability. Among a group of 189 patients with nonpalpable, non-high-grade invasive lesions 15 mm or smaller without lymph/vascular invasion, only 6 (3%) had metastases to lymph nodes. If any three of the favorable factors were present, lymph node positivity was 6% or less. Clinical and pathologic feature of the primary lesions can be used to estimate the risk of axillary lymph node metastases. Such risk assessment can be used for the treatment decision-making process.