Multiregion whole-exome sequencing of matched primary and metastatic tumors revealed genomic heterogeneity and suggested polyclonal seeding in colorectal cancer metastasis.

BACKGROUND: Distant metastasis accounts for 90% of deaths from colorectal cancer (CRC). Genomic heterogeneity has been reported in various solid malignancies, but remains largely under-explored in metastatic CRC tumors, especially in primary to metastatic tumor evolution. PATIENTS AND METHODS: We conducted high-depth whole-exome sequencing in multiple regions of matched primary and metastatic CRC tumors. Using a total of 28 tumor, normal, and lymph node tissues, we analyzed inter- and intra-individual heterogeneity, inferred the tumor subclonal architectures, and depicted the subclonal evolutionary routes from primary to metastatic tumors. RESULTS: CRC has significant inter-individual but relatively limited intra-individual heterogeneity. Genomic landscapes were more similar within primary, metastatic, or lymph node tumors than across these types. Metastatic tumors exhibited less intratumor heterogeneity than primary tumors, indicating that single-region sequencing may be adequate to identify important metastasis mutations to guide treatment. Remarkably, all metastatic tumors inherited multiple genetically distinct subclones from primary tumors, supporting a possible polyclonal seeding mechanism for metastasis. Analysis of one patient with the trio samples of primary, metastatic, and lymph node tumors supported a mechanism of synchronous parallel dissemination from the primary to metastatic tumors that was not mediated through lymph nodes. CONCLUSIONS: In CRC, metastatic tumors have different but less heterogeneous genomic landscapes than primary tumors. It is possible that CRC metastasis is, at least partly, mediated through a polyclonal seeding mechanism. These findings demonstrated the rationale and feasibility for identifying and targeting primary tumor-derived metastasis-potent subclones for the prediction, prevention, and treatment of CRC metastasis.

Neutrophil to lymphocyte ratio associated with prognosis of lung cancer.

PURPOSE: Many studies recently focus on complicated and expensive genomic tests, but the prognostic values of biochemical markers which are easily obtained in clinics are largely overlooked and without further exploration. This study assesses the association of neutrophil-lymphocyte-ratio (NLR) with prognosis of lung cancer patients. METHODS: In 1032 patients with histologically confirmed lung cancer, the association of pretreatment NLR values with overall survival (OS) was evaluated using a Cox proportional hazards model and the temporal relationship of longitudinal NLR was assessed using a mixed effects model. RESULTS: Compared to the patients with a low pretreatment NLR value, those with elevated NLR exhibited a statistically significant worse OS with a hazard ratio (HR) of 1.50 (P < 0.0001) after adjusting for age, gender, race, smoking status, drinking status, tumor stage, tumor grade, histology, and treatments. A significant trend of increasing HRs along with increasing NLR values was observed. The increased risk of death conferred by pretreatment NLR values reached a peak level around 2 years after diagnosis. Moreover, in longitudinal analysis, we observed a trend of dramatically increased NLR values in patients who died during follow-up, but stable NLR values in those who were still alive, with a significant interaction of death-alive status with follow-up time (P < 0.0001). CONCLUSIONS: Elevated NLR is a potential biomarker to identify lung cancer patients with poor prognosis and should be validated in a future clinical trial.

A randomized controlled trial of a tailored interactive computer-delivered intervention to promote colorectal cancer screening: sometimes more is just the same.

BACKGROUND: There have been few studies of tailored interventions to promote colorectal cancer (CRC) screening. PURPOSE: We conducted a randomized trial of a tailored, interactive intervention to increase CRC screening. METHODS: Patients 50-70 years completed a baseline survey, were randomized to one of three groups, and attended a wellness exam after being exposed to a tailored intervention about CRC screening (tailored group), a public web site about CRC screening (web site group), or no intervention (survey-only group). The primary outcome was completion of any recommended CRC screening by 6 months. RESULTS: There was no statistically significant difference in screening by 6 months: 30%, 31%, and 28% of the survey-only, web site, and tailored groups were screened. Exposure to the tailored intervention was associated with increased knowledge and CRC screening self-efficacy at 2 weeks and 6 months. Family history, prior screening, stage of change, and physician recommendation moderated the intervention effects. CONCLUSIONS: A tailored intervention was not more effective at increasing screening than a public web site or only being surveyed.

A statistical model for HIV-1 sequence classification using the subtype analyser (STAR).

MOTIVATION: HIV-1 antiretroviral drug resistance testing produces large amounts of HIV-1 protease and reverse transcriptase sequences. These provide an excellent resource to study the incidence, spread and clinical significance of HIV-1 subtypes. We have produced a program, Subtype Analyser (STAR) that rapidly and accurately subtypes HIV-1. Here we have determined a robust and statistically validated model for subtype assignment. RESULTS: We have significantly extended our HIV-1 subtyping tool (STAR), such that each query sequence when evaluated against subtype profile alignments, returns a discriminating score based on the ratio of subtype positive to negative amino acid positions. These scores were transformed into a Z-score distribution and evaluated. Of the 141 sequences used to define the subtype alignments, 98% were correctly reclassified. Inclusion of additional recombination detection within STAR increased the detection of known recombinant sequences to 95%. AVAILABILITY: STAR is available as compiled (Linux Fedora 3) or source code from http://pgv19.virol.ucl.ac.uk/download/star_linux.tar CONTACT: p.kellam@ucl.ac.uk SUPPLEMENTARY INFORMATION: http://pgv19.virol.ucl.ac.uk/download/star_supplement

Estrogen, but not testosterone, attenuates methamphetamine-evoked dopamine output from superfused striatal tissue of female and male mice.

The gonadal steroid hormone, estrogen, has the capacity to function as a neuroprotectant against methamphetamine (MA)-induced neurotoxicity of the nigrostriatal dopaminergic system within female, but not male, mice. In an attempt to understand some of the bases for this effect of estrogen, the incipient effects of MA upon evoked dopamine output from superfused striatal tissue fragments of gonadectomized female and gonadectomized as well as intact male mice were evaluated under conditions where estrogen (or testosterone) was present in the medium. The amount of dopamine evoked by MA was significantly reduced when estrogen was co-infused with MA. This attenuation was obtained with striatal tissue fragments of gonadectomized female and gonadectomized and intact male mice. In contrast to estrogen, co-infusion of testosterone failed to produce an overall statistically significant change in MA-evoked dopamine output within superfused striatal tissue fragments of gonadectomized female and male mice. In this way, the gonadal steroid hormones, estrogen and testosterone, exert differential modulatory effects upon MA-evoked dopamine output from superfused striatal tissue fragments. However, similar effects to these gonadal steroid hormones were observed between gonadectomized female and gonadectomized or intact male mice. These data reveal an absence of a sexual dimorphism in striatal responsiveness with regard to estrogen's ability to alter MA-evoked DA output. Accordingly, the sexually dimorphic capacity for estrogen to function as a neuroprotectant may involve a composite of actions upon the nigrostriatal dopaminergic system involving events/sites other than the initial stimulation of dopamine output.

Complete diagnostic evaluation in colorectal cancer screening: research design and baseline findings.

BACKGROUND: While indicated by guidelines, complete diagnostic evaluation, or CDE (i.e., colonoscopy or combined flexible sigmoidoscopy plus barium enema X ray), is often not recommended and performed for persons with an abnormal screening fecal occult blood test (FOBT) result. We initiated a randomized trial to assess the impact of a physician-oriented intervention on CDE rates in primary care practices. METHODS: In 1998, we identified 1,184 primary care physicians (PCPs) in 584 practices whose patients received FOBTs that are mailed annually by a managed care organization screening program. A total of 470 PCPs in 318 practices completed a baseline survey. Practices were randomly assigned either to a Control Group (N = 198) or to an Intervention Group (N = 120). Control Group practices received the screening program. Intervention Group practices received the screening program and the intervention (i.e., CDE reminder-feedback plus educational outreach). Practice CDE recommendation and performance rates are the primary outcomes to be measured in the study. RESULTS: Baseline CDE recommendation and performance rates were low and were comparable in Control and Intervention Group practices (54 to 57% and 39 to 40%, respectively). PCPs in the practices tended to view FOBT screening and CDE favorably, but had concerns about screening efficacy, time involved in CDE, and patient discomfort and adherence. Control Group physicians were more likely than Intervention Group physicians to believe that a mail-out FOBT screening program helps in the practice of medicine. CONCLUSIONS: We were able to enroll a high proportion of targeted primary care practices, measure practice characteristics and CDE rates at baseline, and develop and implement the intervention. Study outcome analyses will take into account baseline differences in practice characteristics.

A dose-ranging study to evaluate the antiretroviral activity and safety of amprenavir alone and in combination with abacavir in HIV-infected adults with limited antiretroviral experience.

OBJECTIVE: To evaluate the antiretroviral activity and safety of multiple escalating doses of amprenavir administered alone, and in combination with abacavir in HIV-1-infected adults. DESIGN: Sixty-two HIV-1-infected subjects were enrolled in a multicentre, open-label, non-randomized, dose-escalating trial. METHODS: Subjects were assigned to one of six dose groups and received amprenavir 300 mg twice daily, 300 mg three times daily, 900, 1050, or 1,200 mg twice daily for 4 weeks. One dose group received amprenavir 900 mg twice daily in combination with abacavir 300 mg twice daily for 4 weeks. Antiretroviral activity was assessed by measuring changes from baseline in plasma HIV-1 RNA levels and CD4 cell counts. Safety was evaluated by monitoring clinical adverse events and changes in laboratory values. Genotypic and phenotypic analyses were performed using ABI sequencing and the recombinant virus assay, respectively. RESULTS: At week 4, amprenavir monotherapy (900, 1,050, or 1,200 mg twice daily) resulted in marked decreases in plasma HIV-1 RNA levels (1.3-1.6 log10 copies/ml), and substantial increases in CD4 cell counts in the two dose groups who received 1,050 mg twice daily (118 x 10(6) cells/mm3) or 1,200 mg twice daily (114 x 10(6) cells/mm3). Amprenavir/abacavir resulted in median plasma HIV-1 RNA reductions of 1.8 log10 copies/ml, and median CD4 cell count increases of 138 x 10(6) cells/mm3. Amprenavir was reasonably well tolerated with few treatment-limiting adverse events. No known active site mutations associated with amprenavir resistance were selected in any of the dose groups, and no significant phenotypic resistance to amprenavir developed during 4 weeks of therapy. CONCLUSIONS: The antiviral effect of amprenavir monotherapy increased with escalating doses, and all amprenavir doses were reasonably well tolerated over 4 weeks of therapy. Amprenavir/abacavir combination therapy elicited a potent antiviral effect. The three highest doses of amprenavir (900, 1,050 and 1,200 mg twice daily) were selected to design subsequent Phase II and III studies that confirmed the safety profile and efficacy of amprenavir in combination regimens and led to the approval of amprenavir in the USA in 1999.

Baseline staging tests in primary breast cancer: a practice guideline.

BACKGROUND: Breast cancer develops in over 7000 women each year in Ontario. These patients will all undergo some staging work-up at diagnosis. The Breast Cancer Disease Site Group of the Cancer Care Ontario Practice Guidelines Initiative reviewed the evidence and indications for routine bone scanning, liver ultrasonography and chest radiography in asymptomatic women who have undergone surgery for breast cancer. METHODS: A systematic review of the published literature was combined with a consensus interpretation of the evidence in the context of conventional practice. RESULTS: There were 11 studies of bone scanning reported between 1972 and 1980, involving a total of 1307 women; bone scans detected skeletal metastases in 6.8% of those with stage I breast cancer, 8.8% with stage II and 24.5% with stage III. A total of 5407 women participated in 9 studies of bone scanning reported between 1985 and 1995; in these studies, bone scans detected skeletal metastases in only 0.5% of women with stage I disease, 2.4% with stage II and 8.3% with stage III. Among 1625 women in 4 studies of liver ultrasonography reported between 1988 and 1993, hepatic metastases were detected in 0% of patients with stage I disease, 0.4% with stage II and 2.0% with stage III. Among 3884 patients in 2 studies of chest radiography published in 1988 and 1991, lung metastases were detected in 0.1% of those with stage I, 0.2% with stage II and 1.7% with stage III. False-positive rates ranged from 10% to 22% for bone scanning, 33% to 66% for liver ultrasonography and 0% to 23% for chest radiography. The false-negative rate for bone scanning was about 10%. RECOMMENDATIONS: The following recommendations apply to women with newly diagnosed breast cancer who have undergone surgical resection and who have no symptoms, physical signs or biochemical evidence of metastases. Routine bone scanning, liver ultrasonography and chest radiography are not indicated before surgery. In women with intraductal and pathological stage I tumours, routine bone scanning, liver ultrasonography and chest radiography are not indicated as part of baseline staging. In women who have pathological stage II tumours, a postoperative bone scan is recommended as part of baseline staging. Routine liver ultrasonography and chest radiography are not indicated in this group but could be considered for patients with 4 or more positive lymph nodes. In women with pathological stage III tumours, bone scanning, liver ultrasonography and chest radiography are recommended postoperatively as part of baseline staging. In women for whom treatment options are restricted to tamoxifen or hormone therapy, or for whom no further treatment is indicated because of age or other factors, routine bone scanning, liver ultrasonography and chest radiography are not indicated as part of baseline staging.

Measuring complete diagnostic evaluation in colorectal cancer screening.

Complete diagnostic evaluation, or CDE (i.e., a colonoscopy or combined barium enema X-ray and flexible sigmoidoscopy) is recommended for individuals who have an abnormal screening fecal occult blood test result. Accurate measures of CDE use are needed in colorectal cancer (CRC) screening programs. This study compares the sensitivity and specificity of different methods for measuring CDE recommendation and performance. We identified 17 primary-care practices with 120 patients who had a positive fecal occult blood test result in a CRC screening program operated by a managed-care organization. Approaches used to measure CDE recommendation and performance included external chart audit (ECA) only; internal chart audit (ICA) only; administrative data review (ADR) of electronic claims data; ICA plus ADR; and ECA plus ADR (the "gold standard"). Sensitivity and specificity of each method were assessed relative to CDE recommendation and performance as measured by ECA plus ADR. For CDE recommendation, sensitivity measures were ECA only, 0.926; ICA only, 0.790; ADR only, 0.617; and ICA plus ADR, 0.901. The specificity of each method for CDE recommendation was no less than 0.95. In terms of CDE performance, sensitivity measures were ECA only, 0.877; ICA only, 0.790; ADR only, 0.877; and ICA plus ADR, 0.965. The specificity of each method for CDE performance was 1.0. The ICA-plus-ADR method was a highly sensitive and specific measure of CDE use. This method should be considered in situations that involve primary-care physician follow-up of patients with abnormal CRC screening test results.

Factors associated with perceived risk in automotive employees at increased risk of colorectal cancer.

Risk perception may be an important motivator of health-related behaviors. To develop effective risk communication messages, it is important to understand both the patterns of association between perceived risk and health-related behaviors as well as the correlates of risk perception. Very little is known about whether correlates of risk perception are similar in cross-sectional data compared with prospective data. Furthermore, there are scant data on consistency of correlates of risk perception across groups who vary in objective medical risk. If correlates differ, it would underscore the need to tailor intervention messages based on subgroup characteristics as well as increase awareness of the limitations of basing intervention messages only on cross-sectional data. We analyzed data on a subset of 5042 employees who participated in The Next Step Trial, a randomized health promotion trial to encourage colorectal cancer screening and dietary change. We restricted our analysis to only those automotive workers who were white, male, and did not have colorectal cancer (4477/5042) and who returned surveys both at baseline (2,684/4,477) and at year 2 of follow-up (1955/2684). Initial analyses detected interactions between a history of polyps and several of the other covariates. Therefore, univariate and multivariable analyses were conducted separately for men with and without a personal history of colorectal polyps. Within each of the four subgroups (those with or without polyps in the baseline or follow-up analyses), we examined associations between perceived risk measured at baseline (cross-sectional analyses) and at year 2 of follow-up (prospective analyses) in relation to intervention group status, demographic, medical history, psychosocial, and worksite characteristics measured at baseline. To assess the predictive ability of the models, we computed sensitivity and specificity as measures of each model's ability to correctly classify men into their respective subgroup. Although there was no association between perceived risk and intervention group status in the four subgroups analyzed, we included intervention group status as a covariate in all analyses. At baseline (cross-sectional analyses) among men with and without a history of polyps, perceived risk was positively associated with family history of colorectal polyps or cancer, family support for screening, and worry about being diagnosed with colorectal cancer. In addition, for men without polyps, perceived risk was positively associated with being a current smoker. At year 2 of follow-up (prospective analyses) for men with and without polyps, perceived risk at year 2 was positively associated with family history and baseline perceived risk and was negatively associated with having a normal screening examination or no examinations during the trial. In addition, for men with polyps, perceived risk was positively associated with belief in the salience and coherence of screening and with intention to be screened and was negatively associated with access to screening at the worksite. Specificity was higher than sensitivity in three of four subgroups and was >65% in all subgroups. Except for family history, messages to influence perceived risk would emphasize different factors, depending on whether associations were based on baseline or follow-up data and depending on whether men reported a personal history of polyps. For example, although intervention messages using baseline data would emphasize the same factors for men with or without polyps, messages based on follow-up data would emphasize psychosocial characteristics, such as salience and coherence of screening and intention for men with a history of polyps but not for men without. Our findings support the need to delineate subgroups in the study population to target and tailor health-related messages based on respondent characteristics. Our findings also underscore the need to base health-related messages on prospective data as well as cross-sectional data to better address health-related beliefs and behaviors.

Depression in Korean immigrants with hepatitis B and related liver diseases.

The authors evaluated 50 Korean immigrants who had chronic viral hepatitis or who were healthy carriers for the hepatitis B virus in terms of the relationships between their depression scores, psychosocial stressors, social support, and biological markers of dysfunction. All participants completed a questionnaire, describing their worries and concerns, and the shortform of the Beck Depression Inventory (BDI-sf). Hepatic transaminases, albumin levels, and prothrombin times were measured during routine clinic follow-up visits and were abstracted from the medical record. Values recorded within 3 months before and within 3 months after the psychiatric interview were correlated with BDI scores. BDI-sf total scores were significantly associated with transaminase elevations (P<0.001) both before and after BDI-sf administration. BDI scores were not associated with other measures of liver dysfunction or other medical causes of depression. Patients with higher BDI-sf total scores had more psychosocial stressors (P = 0.008) and lower Global Assessment of Functioning (GAF) scores (P = 0.000).

Preparatory education for informed decision-making in prostate cancer early detection and treatment.

Patients are expected to assume increased responsibility for self-management in health care. However, little attention has been directed to the problem of preparing individuals to play a more active role in the physician-patient relationship. Preparatory education about prostate cancer early detection and treatment is needed to enable patients to recognize the importance of their role in medical decision-making, voice personal values and preferences related to health care choices, and make informed choices under conditions of uncertainty about possible outcomes. Effective decision aids are needed to facilitate shared decision-making in the context of the physician-patient relationship along the continuum of prostate cancer care. Decision aids for patients have taken the form of informational booklets, scripted telephone counseling, decision boards, educational videotapes, interactive videodiscs, computer programs, and Internet Web sites. The impact of preparatory education and the use of decision aids should be evaluated in terms of change in knowledge and understanding, shifts in decision preferences, health care utilization, and satisfaction with care. The need for this type of patient interaction will grow as technology increases patient access to health care information.

Communicating effectively with the patient and family about treatment options for prostate cancer.

To help the patient with prostate cancer, his family, and his friends, in coping with the diagnosis and its treatment, health care providers need to understand the controversies about treatment options and the impact that such controversies have on medical decision-making. To update health care providers, the authors reviewed all pertinent citations in the medicine database from 1966 to 2000, and in other relevant publications. These resources are also available to our patients through the Internet and other avenues, such as books and magazines. It is the role of the physician to counsel patients about their individual circumstances to allow them to make the best individualized treatment option. Patients who have appropriate information and are actively involved with the decision-making process are, in general, psychologically healthier. Though watchful waiting has no side effects, men must cope psychologically with issues of long-term cancer survivorship. With early detection, men can choose between different treatment options (eg, radiation versus radical prostatectomy). Urinary incontinence, sexual dysfunction, and fatigue are major emotional and physical stressors for this population. Providers of care need to be aware of the psychosocial sequelae of prostate cancer and treatment-related side effects and assist their patients in processing ever-growing data on the management of prostate cancer that technology brings.

HIV type 1 protease cleavage site mutations and viral fitness: implications for drug susceptibility phenotyping assays.

The recombinant virus assay (RVA) is a method for assessing the susceptibility of human immunodeficiency virus type 1 (HIV-1) plasma isolates to antiretroviral drugs. The RVA involves the production of viable virus in vitro by homologous recombination of RT-PCR products from plasma virus with a noninfectious reverse transcriptase (RT) or protease (PR)-deleted cloned HIV-1 provirus. In this study, we have constructed RVA plasmids with contiguous deletions in RT, PR, and the p7/p1 and p1/6 gag protease cleavage sites (CS). The deletions in these plasmids allow generation of recombinant viruses with all loci currently identified as important for resistance to anti-HIV-1 drugs being derived from the clinical isolate, including CS mutations that compensate for the reduced fitness of viruses resistant to protease inhibitors (Doyon et al., J Virol 1996:70:3763-3769). We have also used these new constructs to generate viruses with or without compensatory CS mutations, and examined the effects on fitness. In the case of an indinavir-selected virus, fitness was restored close to that of a wild type virus when a vector deleted in the CS and PR was used. With an amprenavir-selected isolate, virus fitness was incompletely restored by including the CS, and this defect appeared to be partially due to reduced infectivity of the virions. We conclude that the CS mutations were required for optimum detection of resistance in the RVA, but that virus fitness can remain compromised even in the presence of compensatory CS mutations.

African-American men and intention to adhere to recommended follow-up for an abnormal prostate cancer early detection examination result.

OBJECTIVES: To assess the intention of African-American men to have the recommended follow-up in the event of an abnormal prostate cancer early detection examination and to identify the variables that help to explain adherence intention. METHODS: In the spring of 1995, we selected a random sample of 548 African-American men who were patients at the University of Chicago Health Service. The sample included men who were 40 to 70 years of age, did not have a personal history of prostate cancer, and had a working telephone number. A total of 413 men who completed the telephone survey received an invitation to consider undergoing a prostate cancer early detection examination. The survey provided data on personal background characteristics, knowledge, attitudes, and beliefs related to prostate cancer and early detection. Respondents were asked whether they would choose to have the recommended follow-up in the event of an abnormal early detection examination result. Univariate and multivariate analyses of intention to have follow-up were performed. RESULTS: An intention to have the recommended follow-up was reported by 77% of the survey respondents. The results of multivariate analyses revealed that the intention to have the follow-up was positively associated with education beyond high school (odds ratio [OR] 1.9); perceived self-efficacy related to prostate cancer screening (OR 2.1); the belief that prostate cancer can be cured (OR 3.3); the belief that prostate cancer screening should be done in the absence of prostate problems (OR 2.3); and physician support for prostate cancer screening (OR 2.1). CONCLUSIONS: African-American men who have a high school education or less may be at risk of nonadherence to recommended follow-up. Adherence also may be low among men who do not have favorable views of early detection or do not perceive strong physician support for early detection. Research is needed to determine whether intention and other factors predict actual adherence to follow-up in this population group.

Biopsychosocial aspects of prostate cancer.

Prostate cancer early detection choices and treatment options are fraught with controversy. To update the consultation-liaison psychiatrist who works with at-risk men, the authors reviewed all pertinent citations in the medicine database from 1966 to 1998 and in other relevant publications. Though watchful waiting for early-stage prostate cancer has no side effects, men must cope psychologically with issues of long-term cancer survivorship. Men can choose between different treatment options (e.g., radiation vs. radical prostatectomy) with early detection. Urinary incontinence, sexual dysfunction, and fatigue are major emotional and physical stressors for this population. Consultation-liaison psychiatrists and physicians need to be aware of the psychosocial sequelae of both prostate cancer and treatment-related side effects.

Hypoglycemic brain injury: potentiation from respiratory depression and injury aggravation from hyperglycemic treatment overshoots.

Hypoglycemia can cause brain dysfunction, brain injury, and death. The present study seeks to broaden current information regarding mechanisms of hypoglycemic brain injury by investigating a novel etiology. The cat's high resistance to brain injury from hypoglycemia suggested that additional influences such as respiratory depression might play a facilitating role. Three groups of cats were exposed to fasting and insulin-induced hypoglycemia (HG; n = 6), euglycemic respiratory depression (RD; n = 5), and combined hypoglycemic respiratory depression (HG/RD; n = 10). The HG animals were maintained at <1.5 mmol (mean 1 mmol) serum glucose concentration for 2 to 6.6 hours. The respiratory depression was associated with PaO2 and PaCO2 values of approximately 50 mm Hg for 1 hour and of approximately 35 and approximately 75 mm Hg, respectively, for the second hour. Magnetic resonance diffusion-weighted imaging estimated brain energy state before, during, and after hypoglycemia. The hypoglycemic respiratory depression exposures were terminated either to euglycemia (n = 4) or to hyperglycemia (n = 6). Brain injury was assessed after 5 to 7 days of survival. Cats exposed to hypoglycemia alone maintained unchanged diffusion coefficients; that is, they lacked evidence of brain energy failure and all six remained brain-intact. Only 1 of 5 euglycemic RD but 10 of 10 HG/RD cats developed brain damage (HG and RD vs. HG/RD, P < 0.01). This difference in brain injury rates suggests injury potentiation by hypoglycemia and respiratory depression acting together. Three injury patterns emerged, including activation of microglia, selective neuronal necrosis, and laminar cortical necrosis. Widespread activation of microglia suggesting damage to neuronal cell processes affected all damaged brains. Selective neuronal necrosis affecting the cerebral cortex, hippocampus, and basal ganglia was observed in all but one case. Instances of laminar cortical necrosis were limited to cats exposed to hypoglycemic respiratory depression treated with hyperglycemia. Thus, treatment with hyperglycemia compared with euglycemia after hypoglycemic respiratory depression exposures significantly increased the brain injury scores (24 +/- 6 vs. 13 +/- 2 points; P < 0.05). This new experimental hypoglycemia model's contribution lies in recognizing additional factors that critically define the occurrence of hypoglycemic brain injury.

Intention to be tested for prostate cancer risk among African-American men.

This study was conducted to identify factors associated with intention to be tested for prostate cancer risk among African-American men. Participants in this study included African-American men (n = 548) who were patients at the University Health Service at the University of Chicago, were 40 to 70 years of age, and did not have a personal history of prostate cancer. Baseline telephone survey data were collected for 413 (75%) men. Respondents were asked if they intended to have a blood test to assess prostate cancer risk. Univariate and multivariate analyses of intention to be tested for risk were performed. Eighty-six percent of the men said that they intended to be tested. Multivariate analysis results show that belief in the efficacy of prostate cancer screening [odds ratio (OR) = 3.6; 95% confidence interval (CI) = 1.4, 9.1] and intention to undergo a prostate cancer-screening (i.e., digital rectal examination and prostate-specific antigen testing; OR = 2.8; 95% CI = 1.3, 6.3) were positively associated with intention to be tested for prostate cancer risk. Being older (OR = 0.4; 95% CI = 0.2, 0.9), having had a prostate cancer-screening examination in the past year (OR = 0.5; 95% CI = 0.2, 1.0), perceiving one's prostate cancer susceptibility to be high (OR = 0.4; 95% CI = 0.2, 0.8), and being fatalistic about prostate cancer prevention (OR = 0.3; 95% CI = 0.2, 0.7) were negatively associated with intention to be tested for risk. Intention to be tested for prostate cancer risk was high among men in the study. Past screening, perceived susceptibility, and beliefs related to early detection might influence receptivity to genetic testing for prostate cancer risk.

African American men, prostate cancer early detection examination use, and informed decision-making.

It is well known that African American men are more likely to be diagnosed with metastatic prostate cancer than White men. Racial variation in the use of prostate cancer early detection modalities (ie, digital rectal examination [DRE] and prostate-specific antigen [PSA] testing) has been suggested as a major reason for this differential. Several factors may help to explain the reported low levels of DRE and PSA test utilization among African American men, including background sociodemographic characteristics, medical history, and cognitive and psychosocial perceptions. In this review, the impact of these characteristics on prostate cancer early detection examination utilization is explored. Findings from studies showing race-related differences in cognitive and psychosocial factors are presented. Preparatory education for informed decision-making is suggested as an approach to help minimize racial differences in cognitive and psychosocial factors that influence the use of prostate cancer early detection modalities. The need to facilitate informed decision-making along the continuum of care is highlighted.