Gradient equivalent crystal theory.

This paper presents an extension of the formalism of equivalent crystal theory (ECT) by introducing an electron density gradient term so that the total model density becomes a more accurate representation of the real local density. Specifically, we allow for the electron density around a lattice site to have directionality, in addition to an average value, as assumed in ECT. We propose that an atom senses its neighbouring density as a weighted sum-the weights given by the its own electronic probability. As a benchmark, the method is used to compute vacancy migration energy curves of iron. These energies are in good agreement with previously published results.

Predictors of advanced stage colorectal cancer diagnosis: results of a population-based study.

While colon cancer is a leading cause of morbidity and mortality among men and women, little is known about demographic variables associated with advanced stage diagnosis at diagnosis. We examined the relationship of age, gender, income, education, marital status, smoking status, urban versus rural residence, and proximal versus distal tumor location on stage at diagnosis. Data from Florida statewide cancer registry for the year 1994 with over 8,933 cases of colorectal cancer was analyzed. Using multivariate analysis, an odds ratio of being diagnosed with advanced stage disease was determined for each demographic variable. We found a significantly increased probability (P < .05) of diagnosis with advanced stage disease for distal lesions in middle-aged persons, smokers, and those with higher education or lower income status. If these findings are verified, they may suggest a group that warrants targeted screening intervention or programs over and above today's current colorectal screening recommendations.

Comorbid illness and the early detection of cancer.

BACKGROUND: Comorbidity may be associated with later detection of cancer. METHODS: Incident cases of colorectal, breast, and prostate cancer and melanoma were determined from the 1994 Florida state tumor registry (N = 32,074). The relationship between comorbidity and late stage at diagnosis was examined using multiple logistic regression. RESULTS: Patients with comorbid conditions had greater odds of late stage diagnosis for each of the four cancers (colorectal, melanoma, breast, and prostate). Higher mortality rates were observed among patients with comorbid illness, not as a result of later stage at diagnosis, but rather due to their underlying disease. CONCLUSIONS: Comorbidity was associated with later stage diagnosis. Further research is needed to determine mechanisms by which comorbidity might influence stage at diagnosis.

Predictors of proximal vs. distal colorectal cancers.

BACKGROUND: Because proximal colorectal cancers have a tendency to present at a more advanced stage and thus have a poorer prognosis, it is important to understand the factors associated with the development of proximal colorectal cancer. We hypothesized that older age, female gender, and the presence of comorbid illness would be associated with proximal cancers. METHODS: Incident cases of colorectal cancer (n = 9,550) occurring in 1994 were identified from Florida's population-based statewide cancer registry. We categorized colorectal cancers as either proximal (cecum, ascending colon, and transverse colon) or distal (descending colon, sigmoid colon, rectosigmoid, and rectum). Multiple logistic regression analysis was used to determine the multivariable relationship between clinical characteristics and the odds of a proximal-occurring lesion. RESULTS: Four characteristics emerged as independent predictors of a proximal lesion. Each year of increasing age was associated with a 2.2 percent increase in the odds of a proximal lesion, whereas female gender was associated with a 38 percent increase in the odds of a proximal lesion. The presence of a comorbid condition was associated with a 28 percent greater odds of a proximal lesion, and, finally, black, non-Hispanic race was associated with a 24 percent greater odds of a proximal lesion. CONCLUSIONS: We found that increasing age, female gender, black, non-Hispanic race, and the presence of comorbid illnesses were factors associated with a greater likelihood of developing colorectal cancer in a proximal location. Further studies will be required to confirm these findings and to establish the mechanism by which comorbidity influences the site of colorectal cancer development.

Bacterial lipopolysaccharide and tumor necrosis factor alpha synergistically increase expression of human endothelial adhesion molecules through activation of NF-kappaB and p38 mitogen-activated protein kinase signaling pathways.

One of the recognized associations of bacterial infection with cardiovascular events is the activation of endothelium and upregulation of adhesion molecules. The two major proinflammatory mediators implicated in the causation of cardiovascular events, bacterial lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF), were found to cooperate to enhance the adhesive properties of endothelial cells. These caused synergistic upregulation of intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 in human umbilical vein endothelial cells as determined by flow cytometry analysis and enzyme-linked immunosorbent assay. This synergism was not due to TNF causing an upregulation of CD14 expression. Treatment with both LPS and TNF resulted in a marked increase in the translocation of NF-kappaB into the nucleus. The activity of p38 mitogen-activated protein kinase was also synergistically enhanced, while the activity of c-jun N-terminal kinase was increased in an additive manner. The results demonstrate that LPS and TNF act synergistically to upregulate the expression of endothelial cell adhesion molecules, possibly by amplification of signaling pathways upstream of transcription. These findings have implications for the understanding of the acceleration of atherosclerotic events seen in low-grade infections with gram-negative organisms.

Effects of physician supply on early detection of breast cancer.

BACKGROUND: There are few studies examining the effects of physician supply on health-related outcomes. We hypothesized that increasing physician supply and, in particular, increasing primary care supply would be related to earlier detection of breast cancer. METHODS: Information on incident cases of breast cancer occurring in Florida in 1994 (n = 11,740) was collected from the state cancer registry. Measures of physician supply were obtained from the 1994 AMA Physician Masterfile. The effects of physician supply on the odds of late-stage diagnosis were examined using multiple logistic regression. RESULTS: There was no relation between overall physician supply and stage of breast cancer of diagnosis. Each 10th percentile increase in primary care physician supply, however, resulted in a 4% increase in the odds of early-stage diagnosis (adjusted odds ratio = 1.04, 95% confidence interval = 1.01-1.06). CONCLUSIONS: The supply of primary care physicians was significantly associated with earlier stage of breast cancer at diagnosis. This study suggests that an appropriate balance of primary care and specialty physician supply might be an important predictor of health outcomes.

Effects of health insurance and race on colorectal cancer treatments and outcomes.

OBJECTIVES: We hypothesized that health insurance payer and race might influence the care and outcomes of patients with colorectal cancer. METHODS: We examined treatments received for all incident cases of colorectal cancer occurring in Florida in 1994 (n = 9551), using state tumor registry data. We also estimated the adjusted risk of death (through 1997), using proportional hazards regression analysis controlling for other predictors of mortality. RESULTS: Treatments received by patients varied considerably according to their insurance payer. Among non-Medicare patients, those in the following groups had higher adjusted risks of death relative to commercial fee-for-service insurance: commercial HMO (risk ratio [RR] = 1.40; 95% confidence interval [CI] = 1.18, 1.67; P = .0001), Medicaid (RR = 1.44; 95% CI = 1.06, 1.97; P = .02), and uninsured (RR = 1.41; 95% CI = 1.12, 1.77; P = .003). Non-Hispanic African Americans had higher mortality rates (RR = 1.18; 95% CI = 1.01, 1.37; P = .04) than non-Hispanic Whites. CONCLUSIONS: Patients with colorectal cancer who were uninsured or insured by Medicaid or commercial HMOs had higher mortality rates than patients with commercial fee-for-service insurance. Mortality was also higher among non-Hispanic African American patients.

Increasing supplies of dermatologists and family physicians are associated with earlier stage of melanoma detection.

BACKGROUND: Physicians are important in the early detection of melanoma. We investigated whether primary care physician supply and the supply of dermatologists were related to stage at diagnosis for malignant melanoma. METHODS: From the state tumor registry in Florida in 1994, we identified incident cases of malignant melanoma for which stage at diagnosis was available (N = 1884). Data on physician supply was obtained from the 1994 American Medical Association Physician Masterfile. Logistic regression determined the effects of physician supply (at the ZIP code level) on the odds of early-stage diagnosis controlling for patients' age, gender, race/ethnicity, marital status, education level, income level, comorbidity, and type of health insurance. RESULTS: Each additional dermatologist per 10,000 population was associated with a 39% increased odds of early diagnosis (odds ratio = 1.39, 95% confidence interval [CI] 1.09-1.70, P =.010). For each additional family physician per 10,000 population, the odds of early diagnosis increased 21% (odds ratio = 1.21, 95% CI 1.09-1.33, P <.001). Each additional general internist per 10,000 population was associated with a 10% decrease in the odds of early-stage diagnosis (odds ratio = 0.90, 95% CI 0.83-0.98, P =.009). The supplies of general practitioners, obstetrician/gynecologists, and other nonprimary care specialists were not associated with stage at diagnosis. CONCLUSIONS: Increasing supplies of dermatologists and family physicians were associated with earlier detection of melanoma. In contrast, increasing supplies of general internists were associated with reduced odds of early detection. Our findings suggest that the composition of the physician work force may affect important health outcomes and needs further study.

The use and outcomes of outpatient mastectomy in Florida.

BACKGROUND: To identify patient characteristics associated with outpatient mastectomies and their outcomes. METHODS: Patients diagnosed with breast cancer and treated with mastectomies in Florida in 1994 were identified from state discharge abstracts and the state tumor registry. The relationship between clinical/demographic characteristics and the odds of having an outpatient mastectomy was identified using multiple logistic regression. Outcomes were assessed by calculating the risk of being rehospitalized within 30 days of discharge. RESULTS: Twenty percent of mastectomies were performed on an outpatient basis. Outpatient mastectomies were more likely to be performed on women who were older, who lived in higher income communities, or who were uninsured. Health insurance type was not associated with having an outpatient mastectomy. Women undergoing outpatient mastectomy were more likely to be readmitted within 30 days of discharge; however, the excess risk was very small (0.7%). CONCLUSIONS: The risks from outpatient mastectomy are small. Ongoing monitoring of outcomes and assessment of patient satisfaction are needed.

Demographic predictors of melanoma stage at diagnosis.

OBJECTIVE: To examine sociodemographic characteristics as possible predictors of late-stage melanoma diagnosis. We hypothesized that late-stage diagnosis would be associated with the following: older age, male sex, unmarried status, lower educational attainment and income level, rural residence, and cigarette smoking. METHODS: We used data from the state tumor registry to study all incident cases of melanoma occurring in Florida during 1994 whose stage at diagnosis was available (N = 1884). We used multiple logistic regression to determine the effects of sociodemographic characteristics on the odds of late-stage (regional or distant metastases) diagnosis. RESULTS: There were 243 patients (12.9%) diagnosed as having melanoma that had metastasized to either regional lymph nodes or distant sites. Patients who were unmarried (odds ratio, 1.5; P= .01), male (odds ratio, 2.2; P<.001), or smokers (odds ratio, 2.2; P<.001) or who resided in communities with lower median educational attainment (odds ratio, 1.5; P= .048) had greater odds of having a late-stage diagnosis. CONCLUSIONS: To detect these cancers at an earlier stage and improve outcomes, there should be increased educational efforts directed toward physicians who treat these patients. A recognition that there may be additional risk factors for late-stage diagnosis, beyond the established risk factors, such as family history and excess sun exposure, should be included in the initial assessment. Specific public education efforts should also be targeted to these patients to increase their self-surveillance and surveillance of their partners.

Clinical and demographic predictors of late-stage cervical cancer.

BACKGROUND: Despite increasingly widespread use of the Papanicolaou smear, almost half of all women with invasive cervical cancer are diagnosed at a late stage (regional or distant). Little is known about factors associated with late-stage diagnosis of cervical cancer. OBJECTIVE: To examine the relationship of age, race, education level, income level, smoking, marital status, health insurance type, comorbidity, and residence in an urban or rural setting to late stage at diagnosis of cervical cancer. METHODS: Incident cases of invasive cervical cancer occurring in 1994 in Florida were identified from the state tumor registry (N = 852). Cases were linked with state discharge abstracts and the 1990 US census. Multiple logistic regression was used to determine the relationship between predictor variables (age, race or ethnicity, marital status, smoking status, education level, income level, insurance type, comorbidity, and urban vs rural residence) and the odds of late-stage diagnosis. RESULTS: Age, marital status, and insurance type were associated with late-stage diagnosis. Each additional year of age was associated with a 3% increased odds of late-stage diagnosis (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.02-1.05; P<.001). Being unmarried was associated with a 63% increased odds of late-stage diagnosis (OR, 1.63; 95% CI, 1.18-2.25; P=.003). Being uninsured was associated with a 60% increased odds of late-stage diagnosis (OR, 1.60; 95% CI, 1.07-2.38; P=.02). Having commercial health maintenance organization insurance was associated with a 46% decreased odds of late-stage disease (OR, 0.54; 95% CI, 0.30-0.96; P=.04). Race, education level, income level, smoking status, comorbidity, and urban residence were not associated with stage at diagnosis. CONCLUSIONS: Women with cervical cancer who are elderly, unmarried, and uninsured are more likely to be diagnosed at a late stage. These women should be targeted for cervical cancer education and screening programs.

Comparing the toxicity of digoxin and digitoxin in a geriatric population: should an old drug be rediscovered?

BACKGROUND: Little information is available regarding toxicity rates of the two available forms of cardiac glycosides (digoxin, digitoxin) when used in elderly patients. METHODS: We retrospectively analyzed the charts of all patients more than 60 years of age who were chronically managed with a cardiac glycoside and were hospitalized during the period January 1995 through January 1998. Toxicity was defined as any clinical event that required either a reduction in dose of the drug or its discontinuance. RESULTS: Toxicity occurred among 7.6% of hospitalizations in which digitoxin was used, compared with 18.3% of hospitalizations in which digoxin was used. In multivariate analysis, the odds of toxicity adjusted for other clinical characteristics were three times greater for patients taking digoxin than for patients taking digitoxin. CONCLUSION: Hospitalized elderly patients taking digitoxin had a lower rate of toxicity than those taking digoxin.

The mouse Nkx-1.2 homeobox gene: alternative RNA splicing at canonical and noncanonical splice sites.

A mouse homeobox gene, Nkx-1.2, (previously termed Sax-1) that is closely related to the Drosophila NK-1/S59 gene was cloned, and genomic DNA and cDNA were sequenced. Nine Nkx-1.2 cDNA clones were found that correspond to three species of Nkx-1.2 mRNA that are formed by alternative splicing at conventional 5' donor and 3' acceptor splice sites; however, seven cDNA clones were found that correspond to three species of Nkx-1.2 mRNA from testes that have novel TG/AC 5' and 3' splice sites. The consensus splice sequences are: 5' donor, CC downward arrowTGGAAG; 3' acceptor, ACTTAC downward arrow. Predicted amino acid sequences suggest that some transcripts may be translated into proteins that lack part or all of the homeodomain. At least three bands of Nkx-1.2 mRNA were found in RNA from the testes. Nkx-1.2 mRNA was shown to be present in postmeiotic germ cells of the testis and in mature spermatozoa. Nkx-1.2 mRNA also was found in regions of the adult cerebral cortex, hippocampus, diencephalon, pons/medulla, and cerebellum. Nkx-1.2 mRNA was found in embryos in highest abundance in 10-day embryos; the mRNA levels decrease during further development. Nkx-1.2 mRNA also was found in discrete zones of the embryonic mesencephalon and myelencephalon.

Effects of health insurance and race on breast carcinoma treatments and outcomes.

BACKGROUND: The authors hypothesized that insurance payer and race would influence the care and outcomes for patients with breast carcinoma. METHODS: The authors examined treatments and adjusted risk of death (through 1997) for all incident cases of breast carcinoma occurring in Florida in 1994 (n = 11,113) by using state tumor registry data. RESULTS: Patients lacking health insurance were less likely to receive breast-conserving surgery (BCS) compared with patients who had private health insurance. Among patients insured by Medicare, those belonging to a health maintenance organization (HMO) were more likely to receive BCS but less likely to receive radiation therapy after BCS. Non-Hispanic African Americans had higher mortality rates even when stage at diagnosis, insurance payer, and treatment modalities used were adjusted in multivariate models (adjusted risk ratio [RR], 1.35; 95% confidence interval [CI], 1.12-1.61; P = 0.001). Patients who had HMO insurance had similar survival rates compared with those with fee-for-service (FFS) insurance. Among non-Medicare patients, mortality rates were higher for patients who had Medicaid insurance (RR, 1.58, 95% CI, 1.18-2.11; P = 0.002) and those who lacked health insurance (RR, 1.31; 95% CI, 1.03-1.68; P = 0.03) compared with patients who had commercial FFS insurance. There were no insurance-related differences in survival rates, however, once stage at diagnosis was controlled. CONCLUSIONS: As a result of later stage at diagnosis, patients with breast carcinoma who were uninsured, or insured by Medicaid, had higher mortality rates. Mortality rates were also higher among non-Hispanic African Americans, a finding that was not fully explained by differences in stage at diagnosis, treatment modalities used, or insurance payer.

Down-regulation of the pharmacokinetic-pharmacodynamic response to interleukin-12 during long-term administration to patients with renal cell carcinoma and evaluation of the mechanism of this "adaptive response" in mice.

BACKGROUND: Interleukin-12 (IL-12) is a cytokine that promotes type-1 helper T-cell responses and may have therapeutic utility in the treatment of cancer, asthma, and a variety of infectious diseases. METHODS: In a phase I trial, recombinant human IL-12 (rHuIL-12) was administered subcutaneously once a week at a fixed dose of 0.1 to 1.0 microg/kg to 24 patients with renal cell carcinoma. A similar study was later performed in mice to evaluate the mechanism of down-regulation of pharmacokinetic-pharmacodynamic response observed in patients with cancer. RESULTS: Adverse events, serum IL-12 levels, and serum levels of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) produced in response to IL- 12 were all maximum in the week after the first dose of rHuIL-12 and decreased after long-term administration. Similar to these results, repetitive subcutaneous administration of recombinant mouse IL-12 (rMoIL-12) to normal mice led to down-regulation of serum levels of IL-12 and IFN-gamma measured 5 hours after rMoIL-12 injection. Down-regulation of IL-12 serum levels was inversely correlated with the up-regulation of IL-12 receptor expression and may be the result of increased clearance of rMoIL-12 from serum by binding to lymphoid cells expressing increased amounts of IL-12 receptor. The down-regulation of serum IFN-gamma levels correlated with decreased IFN-gamma messenger ribonucleic acid expression and may result from feedback inhibition of IL-12 signaling or from a more specific inhibition of IFN-gamma synthesis. CONCLUSION: Administration of rHuIL-12 in fixed weekly doses resulted in decreased serum levels of IL-12 and of IFN-gamma, a secondary cytokine believed to be critical to response of IL-12. A better understanding of the complex regulation of the pharmacokinetic-pharmacodynamic response to IL-12 should facilitate the development of more effective dosing regimens for its use in the clinic.

University students' knowledge and awareness of HPV.

BACKGROUND: The purpose of this study was to evaluate the knowledge, attitudes, and behaviors of university students regarding the human papillomavirus (HPV). METHODS: A random sample of 500 university students was mailed a self-administered questionnaire that elicited their knowledge and awareness about HPV and compared their knowledge and attitudes with those of other sexually transmitted diseases (STDs). Among the 480 deliverable addresses, 289 students responded (response rate 60%). RESULTS: Only 37% of respondents had ever heard of HPV, and the median score on a 13-item knowledge scale was only 3. Of seven STDs assessed, respondents indicated they knew the least about HPV and perceived that this STD has received the least educational effort. In multivariate analyses, predictors of lower knowledge and awareness about HPV were male gender and sexual behavior (having multiple partners, not using condoms). CONCLUSIONS: Despite the high prevalence of HPV among young adults, most students knew very little about this infection. Implementing HPV educational programs and measuring their effectiveness should be a priority.

Structure, properties, and tissue localization of apoplastic alpha-glucosidase in crucifers.

Apoplastic alpha-glucosidases occur widely in plants but their function is unknown because appropriate substrates in the apoplast have not been identified. Arabidopsis contains at least three alpha-glucosidase genes; Aglu-1 and Aglu-3 are sequenced and Aglu-2 is known from six expressed sequence tags. Antibodies raised to a portion of Aglu-1 expressed in Escherichia coli recognize two proteins of 96 and 81 kD, respectively, in vegetative tissues of Arabidopsis, broccoli (Brassica oleracea L.), and mustard (Brassica napus L.). The acidic alpha-glucosidase activity from broccoli flower buds was purified using concanavalin A and ion-exchange chromatography. Two active fractions were resolved and both contained a 96-kD immunoreactive polypeptide. The N-terminal sequence from the 96-kD broccoli alpha-glucosidase indicated that it corresponds to the Arabidopsis Aglu-2 gene and that approximately 15 kD of the predicted N terminus was cleaved. The 81-kD protein was more abundant than the 96-kD protein, but it was not active with 4-methylumbelliferyl-alpha-D-glucopyranoside as the substrate and it did not bind to concanavalin A. In situ activity staining using 5-bromo-4-chloro-3-indolyl-alpha-D-glucopyranoside revealed that the acidic alpha-glucosidase activity is predominantly located in the outer cortex of broccoli stems and in vascular tissue, especially in leaf traces.

The effects of physician supply on the early detection of colorectal cancer.

BACKGROUND: Policymakers question whether there is a relationship between the number and distribution of physicians and the outcomes for important health conditions. We hypothesized that increasing primary care physician supply would be related to earlier detection of colorectal cancer. METHODS: We identified incident cases of colorectal cancer occurring in Florida in 1994 (n = 8,933) from the state cancer registry. We then obtained measures of physician supply from the 1994 American Medical Association Physician Masterfile and examined the effects of physician supply (at the levels of county and ZIP code clusters) on the odds of late-stage diagnosis using multiple logistic regression. RESULTS: For each 10-percentile increase in primary care physician supply at the county level, the odds of late-stage diagnosis decreased by 5% (adjusted odds ratio [OR] = 0.95; 95% confidence interval [CI], 0.92 - 0.99; P = .007). For each 10-percentile increase in specialty physician supply, the odds of late-stage diagnosis increased by 5% (adjusted OR = 1.05; 95% CI, 1.02-1.09; P = .006). Within ZIP code clusters, each 10-percentile increase in the supply of general internists was associated with a 3% decrease in the odds of late-stage diagnosis (OR = 0.97; 95% CI, 0.95 - 0.99; P = .006), and among women, each 10-percentile increase in the supply of obstetrician/gynecologists was associated with a 5% increase in the odds of late-stage diagnosis (OR = 1.05; 95% CI, 1.01 - 1.08; P = .005). CONCLUSIONS: If the relationships observed were causal, then as many as 874 of the 5463 (16%) late-stage colorectal cancer diagnoses are attributable to the physician specialty supply found in Florida. These findings suggest that an appropriate balance of primary care and specialty physicians may be important in achieving optimal health outcomes.

Occult breast cancer detection with technetium-99m-sestamibi: a case report.

A 74-y-old woman with a 4-y history of left arm lymphedema and multiple negative mammography studies presented to her physician with a palpable subcutaneous nodule in the left upper arm. After biopsy the nodule was read pathologically as secondary breast carcinoma. We report a finding of a positive 99mTc-sestamibi scintimammography in the presence of an unremarkable mammogram. The study also revealed a positive uptake in a metastatic lesion in the manubrium of the sternum.