Biomedical subjects

Constantine Daskalakis

Publications and source records attributed to Constantine Daskalakis.

13 recordsLinked to original sources

PubMed2006

Increasing access to clinical and educational studies.

In 2001, the National Cancer Institute (NCI) provided funds to support the Increasing Access to Clinical and Educational Studies (ACES) Project of the Thomas Jefferson University, Kimmel Cancer Center in Philadelphia. The ACES Project enabled the Center to engage in the systematic development of approaches for reducing cancer health disparities among African Americans in Philadelphia. This project brought together community partners, clinical partners, cancer prevention and control experts, and staff from an NCI-designated cancer center to develop and implement a community-based outreach education program, a special populations investigator (SPI) training program, and SPI pilot studies in cancer screening and clinical trials participation. At the end of 5 years, the ACES Project had 1) organized a steering committee, expert panel, and a network of community collaborators and clinical partners; 2) implemented a clinical trials education program for community-based nurses, lay health advocates active in community organizations, and health ministries in community churches; 3) mentored 4 SPIs in cancer prevention and control research; 4) completed SPI pilot studies; and 5) leveraged these activities to gain support for cancer health disparities related research. The Project established a successful dialogue between an NCI-designated cancer center and the African American population related to cancer research, and enabled SPIs from the community to adapt evidence-informed interventions for application in cancer prevention and control research. Lessons learned from the Project can guide the implementation of such projects in the future. Cancer 2006. (c) 2006 American Cancer Society.

Black or African American↗

PubMed2006

Surgeon-performed ultrasound for preoperative localization of abnormal parathyroid glands in patients with primary hyperparathyroidism.

BACKGROUND: The introduction of portable ultrasound equipment enables surgeons to perform ultrasound examinations in a clinic setting. This study was undertaken to evaluate surgeon-performed ultrasound (SP-US) in patients with primary hyperparathyroidism (PHPT). METHODS: Between July 2003 and March 2004, 65 patients with PHPT were evaluated with SP-US and 48 of these patients underwent parathyroid surgery. Among this group of 48 evaluable patients, 47 had preoperative imaging with technetium-99m sestamibi scanning (MIBI), and 12 had an additional ultrasound examination at an external radiology department (RP-US). RESULTS: All patients were cured of PHPT and the operative findings were used to determine the true status of the parathyroid glands of each patient. Twenty-four (50%) patients had concomitant thyroid nodules which were identified by SP-US, and 4 (8.3%) patients had simultaneous thyroid operations, 2 of which were for thyroid cancer. Considering data for all patients, SP-US had significantly higher sensitivity than MIBI or RP-US (60% vs. 46%, P = 0.013, and 60% vs. 11%, P = 0.004 respectively). Among the patients with a single adenoma, SP-US, MIBI, and RP-US had sensitivities of 83%, 63%, and 13% respectively. The specificities of all three imaging techniques were uniformly high and were not significantly different from each other. CONCLUSIONS: Surgeon-performed ultrasound is an accurate modality for localizing abnormal parathyroid glands in patients with PHPT, with results that compare favorably with other parathyroid imaging modalities.

Adenoma↗

PubMed2006

Utility of indices of gun availability in the community.

OBJECTIVE: To estimate the degree to which the proportion of homicides and suicides committed with a gun is associated with reported availability of firearms across Chicago neighbourhoods. METHODS: Data were collected as part of the Project on Human Development in Chicago Neighborhoods (PHDCN), a combined neighbourhood and individual level study of the city of Chicago. The study used data from 837 PHDCN participants between the ages of 17 and 22, residing in 170 different neighbourhoods. Gun availability was measured via participant reports on whether they had carried a gun and whether they perceived gun access to be easy in their community. Data on suicides and homicides were obtained from the Chicago Department of Health. RESULTS: A 10% change in the proportion of homicides committed by a gun in a neighbourhood was associated with a 20% increase in both the odds of reported gun access and reported gun carrying (p=0.002 and 0.048, respectively). The proportion of firearm related suicides was not associated with either of those self reported measures. CONCLUSIONS: The proportion of firearm related homicides, but not the proportion of firearm related suicides, is a useful predictor of gun availability across small areas such as neighbourhoods.

Adolescent↗

PubMed2005

Racial and socioeconomic differences in psychiatric symptoms in nursing home residents: a minimum data set-based pilot study.

BACKGROUND: Little research has explored racial and socioeconomic differences in the presence, detection, and treatment of neuropsychiatric symptoms in nursing home residents. OBJECTIVE: To evaluate racial and socioeconomic differences on mood and behavior Minimum Data Set (MDS) recorded symptoms, MDS recorded psychiatric diagnoses, and MDS identified psychotropic medication use. METHODS: Data were obtained through a cross-sectional review of MDS data of 290 African-American and white residents of 2 nursing homes. The association between age, gender, race, and pay status with mood and behavior patterns, psychiatric diagnoses, and use of psychotropic medication was evaluated. RESULTS: White residents were more likely than African American residents to have MDS recorded psychiatric diagnoses (odds ratio, OR = 3.24), but there were no significant racial differences in recorded mood or behavior symptomatology or in the pharmacologic treatment of mental illness. Medicaid recipients were more likely than nonrecipients to have behavior symptoms (OR = 2.09), have a psychiatric diagnosis (OR = 2.91), and receive psychotropic medications in the absence of a psychiatric diagnosis (OR = 3.62). CONCLUSION: Pay status was associated with recorded symptoms, diagnoses, and medications, but racial differences were found only for recorded diagnoses.

Black or African American↗

PubMed2005

Effect of the tumor vascular-damaging agent, ZD6126, on the radioresponse of U87 glioblastoma.

PURPOSE: The effect of ZD6126 on tumor oxygen tension and tumor growth delay in combination with ionizing radiation was examined in the human U87 glioblastoma tumor model. Resistance to ZD6126 treatment was investigated with the nitric oxide synthase inhibitor, l-N(G)-nitroarginine methyl ester (hydrochloride; l-NAME/active form, l-NNA). METHODS: U87 human xenografts were grown in athymic nude mice. ZD6126 was given with or without l-NNA. Tumor oxygen tension was measured using the Oxford Oxylite (Oxford, England) fiberoptic probe system. Tumor volume was determined by direct measurement with calipers and calculated by the formula [(smallest diameter(2) x widest diameter)/2]. RESULTS: Multiple doses of ZD6126 treatment (three doses) had a significant effect on tumor growth delay, reducing the average daily tumor growth rate from 29% to 16%. When given 1 hour before radiation, ZD6126 caused an acute increase in hypoxia in U87 tumors, and reduced tumor growth delay compared with that of radiation alone. The combination of ZD6126 given after radiation, either as a single dose or in multiple doses, had greater or similar antitumor activity compared with radiation alone. Twenty-four hours after administration, a single dose of ZD6126 induced little (10 +/- 8%) necrosis in U87 xenografts. l-NNA, when given in combination with ZD6126, significantly enhanced the effectiveness of ZD6126 in inducing tumor necrosis. CONCLUSIONS: Our observation that ZD6126-induced tumor hypoxia can decrease radiation response when ZD6126 is given prior to radiation indicates the importance of scheduling. Our findings suggest that the optimal therapeutic benefit of ZD6126 plus radiation in human glioblastoma may require multiple dosing in combination with a nitric oxide synthase inhibitor, to be scheduled following radiotherapy.

Angiogenesis Inhibitors↗

PubMed2005

GATA-3 expression as a predictor of hormone response in breast cancer.

BACKGROUND: Expression of estrogen receptor-alpha (ERalpha) as determined by immunohistochemistry of tumor tissue is currently the most clinically useful test to predict hormone responsiveness of breast cancer. Thirty percent of ERalpha-positive breast cancers do not respond to hormonal therapy. GATA-3 is a transcription factor that is expressed in association with ERalpha and there is evidence that GATA factors influence response to estrogen. In this pilot study, we investigated whether GATA-3 expression is associated with hormone response in breast cancer. STUDY DESIGN: Breast cancer tissue was stained for GATA-3 expression by immunohistochemistry in ERalpha-positive cancers from 28 patients, 14 of whom were defined as hormone unresponsive (cases) and 14 of whom were age-matched controls with hormone-responsive, ERalpha-positive cancers (controls). RESULTS: Comparing cases and controls, there were no differences in expression of ERalpha; progesterone receptor, ErbB2; or tumor grade. Using 20% nuclear staining to characterize tumors as GATA-3 positive or GATA-3 negative, 6 of 14 (43%) cancers in the hormone-unresponsive group and none of the controls were classified as GATA-3 negative (odds ratio, 8.2; 95% confidence interval, 1.2-infinity; p = 0.031). Using different cut points to characterize GATA-3 positivity yielded very similar results, indicating a positive association between lack of GATA-3 expression and lack of response to hormonal therapy. CONCLUSIONS: The study suggests that analyzing ERalpha-positive breast tumors for GATA-3 using immunohistochemistry might improve prediction of hormone responsiveness. The association between GATA-3 expression and hormone response suggests that GATA-3 may play a role in mechanisms controlling response to estrogen.

Adult↗

PubMed2005

Preparing African-American men in community primary care practices to decide whether or not to have prostate cancer screening.

BACKGROUND: This study was a randomized trial to test the impact of an informed decision-making intervention on prostate cancer screening use. METHODS: The study population included 242 African-American men from three primary care practices who were 40-69 years of age and had no history of prostate cancer. Participants completed a baseline survey questionnaire and were randomly assigned either to a Standard Intervention (SI) group (N=121) or an Enhanced Intervention (EI) group (N=121). An informational booklet was mailed to both groups. EI group men were also offered a screening decision education session. Two outcomes were considered: (1) complete screening (i.e., having a digital rectal exam (DRE) and prostate specific antigen (PSA) testing), and (2) complete or partial screening (i.e., having a PSA test with or without DRE). An endpoint chart audit was performed six months after initial intervention contact. The data were analyzed via exact logistic regression. RESULTS: Overall, screening use was low among study participants. EI group men had a screening frequency two times greater than that of SI group men, but the difference was not statistically significant: 8% vs. 4 % (OR = 1.94) fo rcomplete screening, and 19% vs. 10% (OR = 2.08) for complete or partial screening. Multivariable analyses showed that being in the EI group and primary care practice were significant predictors of complete or partial screening (OR = 3.9 and OR = 5.64, respectively). CONCLUSION: Prostate cancer screening use may be influenced by exposure to decision education and the influence of screening-related primary care practice factors.

Adult↗

PubMed2004

Smoking prevention: implications of study design, research setting, and goals.

Collaborations among various disciplines concerned with smoking prevention are gaining in currency. Such collaborations are predicated, in part, on recognizing both the implicit assumptions in different fields and the consequences of these assumptions. These issues, however, are often ignored in transdisciplinary research. In this article, we demonstrate how simple indices, such as the risk ratio, attributable fraction, or R(2), may have different implications for causal inference and interventions, depending on study setting and research goals.

Humans↗

PubMed2004

Behaviors used by men to protect themselves against prostate cancer.

This paper reports on behaviors men use to protect themselves against prostate cancer. Data were collected via a telephone or mailed survey from 353 men enrolled in two studies of prostate cancer screening. Respondents reported behaviors they used to protect themselves against prostate cancer, and responses were coded as conventional care, self-care, or nothing. Men who reported using both conventional care and self-care were categorized as conventional care users. Polytomous logistic regression was conducted to evaluate the association between sociodemographic background, prior prostate screening, and cognitive, affective, and social support and influence factors with protective behavior type. The distribution of protective behaviors was as follows: conventional care, 63%; self-care only, 19%; and nothing, 18%. In multivariable analyses, higher education level was found to be positively associated with conventional care use. Perceived salience and coherence of prostate cancer screening was positively associated with conventional care use among men in one of the two studies. Low concern about screening was positively associated with self-care use, as was mailed survey completion. This study presents self-report data regarding prostate cancer protection behaviors. Most men in the study reported using some type of prostate cancer protective behavior. Decision-making about whether or not to take protective action and what type of behavior to use may be influenced by socioeconomic background, cognitive perceptions related to behavioral options, and concern about risk.

Adult↗

PubMed2003

Tumor oxygenation and acidification are increased in melanoma xenografts after exposure to hyperglycemia and meta-iodo-benzylguanidine.

Tumor oxygen tension and extracellular pH (pH(e)) are physiological parameters that can be manipulated to improve current cancer therapies. Many human tumors consist of cells that are chronically exposed to low pH(e). Exposure of tumor cells in culture to glucose decreases oxygen consumption (oxygen sparing or Crabtree effect), and while this effect is absent in low pH-adapted tumor cells, it can be restored by combining the respiratory inhibitor meta-iodo-benzylguanidine (MIBG) with glucose (Burd et al., Cancer Res. 61, 5630-5635, 2001). The effects of hyperglycemia and MIBG on tumor oxygen tension and on pH(e) were investigated in human melanoma xenografts in SCID mice. An oral gavage of 1 M glucose (2 g/kg) increased the average blood glucose concentration from <140 mg/dl to approximately 400 mg/dl. Although tumor pH(e) decreased from pH 6.7 to pH 6.5 (P < 0.01) after about 60 min, no change in tumor oxygen tension was observed. However, when oral glucose and MIBG (15 mg/kg) were administered together, oxygen tension increased from 2.8 mmHg to approximately 17 mmHg, and tumor pH(e) decreased from pH 6.7 to pH 6.3 (P < 0.01) after about 115 min. In conclusion, administration of glucose together with MIBG increases tumor oxygen tension and also increases the magnitude and duration of acidification. Hyperglycemia plus MIBG has the potential to improve response to radiation therapy as well as to hyperthermia and some chemotherapies.

Animals↗

PubMed2003

Intracellular acidification abrogates the heat shock response and compromises survival of human melanoma cells.

This study tests the hypothesis that lowering intracellular pH (pHi) in melanoma cells grown at low extracellular pH (pHe) selectively abrogates 42 degrees C-induced heat shock protein (HSP) expression and reduces survival. Cells were acidified by a combination of a 0.2-pH-unit decrease in pHe coupled with the lactate/H+ transport inhibitor alpha-cyano-4-hydroxy-cinnamic acid (CNCn). A mild acute extracellular acidification was used to mimic the acute extracellular acidification observed in tumors that can be induced in vivo by oral glucose administration. CNCn blocks the activity of H(+)-linked monocarboxylate transporters (MCTs), particularly MCT isoform 1 (MCT-1). This transporter removes lactic acid from cells and has a high activity in DB-1 melanoma cells grown at low pHe. The effect of extracellular acidification combined with CNCn on pHi was measured in cells grown at pHe 6.7 and pHe 7.3. Cells grown at pHe 6.7 serve as an in vitro model for cells in an acidic tumor microenvironment. When cells were grown at pHe 6.7 and incubated with CNCn at pHe 6.5, the pHi decreased from 6.9 to below 6.5, and the 42 degrees C induction of HSP70 and HSP27 was blocked. The abrogation of HSP induction correlated positively with decreased clonogenic survival. In contrast, when cells growing at pHe 7.3 were acidified by a 0.2-pH unit to pHe 7.1, the inhibitor had less effect on pHi, which remained above 7.0. Under these conditions, the 42 degrees C-induction of HSPs was not inhibited, and cytotoxicity was not enhanced. These results indicate that a significant decrease in the pHi of melanoma cells can selectively sensitize the cells to 42 degrees C hyperthermia, possibly through the inhibition of HSP expression. This strategy could result in a therapeutic gain, because normal tissues, existing at a pHe above 7.0, would not be sensitized.

Blotting, Western↗

PubMed2003

The cyclooxygenase-2 inhibitor, celecoxib, prevents the development of mammary tumors in Her-2/neu mice.

Evidence is now available showing that cyclooxygenase (COX)-2, which is involved in prostaglandin production, is overexpressed in many types of tumors including breast. Several reports have indicated that HER-2/neu-positive breast tumors are associated with an increased amount of COX-2 protein. In this study, we evaluated the effectiveness of the select COX-1 and COX-2 inhibitors in preventing mammary tumor development in HER-2/neu transgenic mice. At 4 weeks of age, female HER-2/neu mice were fed a #5020 rodent diet supplemented with 900 ppm celecoxib, a COX-2 inhibitor, 64 ppm of SC560, a COX-1 inhibitor, or the unsupplemented #5001 diet (control). The incidence of mammary tumors was significantly lower in the celecoxib-fed mice (71%; P = 0.001 versus control) than in the control mice (95%) or in the SC560-fed mice (91%). Celecoxib-treated mice also developed fewer tumors (1.3 +/- 1.1 SD; P = 0.039 versus control) than the control mice (2.2 +/- 1.2) or the SC560 treated mice (2.3 +/- 1.3). The median time to tumor development was 266 days in the control group versus 291 days in the celecoxib-treated group (P = 0.003 versus control). Lung metastasis was also reduced by treatment with celecoxib. The COX-1 inhibitor SC560 had no protective effect. The protection offered by celecoxib was associated with significantly lower concentrations of prostacyclin and prostaglandin E(2) in mammary tumors and their adjacent mammary glands. Our findings provide additional preclinical evidence to support the clinical studies to investigate the potential effectiveness of COX-2 inhibitors in protecting woman who are at high risk for breast cancer.

Animals↗

PubMed2002

Regression analysis of multiple-source longitudinal outcomes: a "Stirling County" depression study.

Epidemiologic studies of psychiatric disorders have increasingly relied on multiple sources of information to improve the validity of diagnoses and repeated assessments over time to provide a longitudinal perspective. In this paper, the authors present a general multivariate logistic regression method for the simultaneous analysis of discrete outcomes that exhibit such features. This approach permits risk factor and agreement analyses within a unified framework and appropriately uses data from subjects who may be missing some outcomes. The authors use this approach to analyze data from a "Stirling County" study of depression. During a 3- to 4-year period in the early 1990s, 631 subjects were assessed in two separate interviews, on each occasion with two diagnostic schedules (the DePression and AnXiety schedule (DPAX) and the Diagnostic Interview Schedule (DIS)). The female:male ratio of depression was found to be different for the DPAX and the DIS (0.8 and 1.6, respectively). Education was inversely associated with depression, while the effects of time, the subject's age, and the interviewer's sex were essentially null. With respect to the outcomes' association, agreement between the DPAX and the DIS was low. In addition, stability of the DPAX over time was significantly higher than that of the DIS. No covariates were found to affect significantly the association between outcomes.

Adult↗