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Biomedical subjects

B Cole

Publications and source records attributed to B Cole.

At least 19 recordsLinked to original sources
PubMed2006

Ex vivo expansion of non-MHC-restricted cytotoxic effector cells as adoptive immunotherapy for myeloma.

BACKGROUND: PBMC can be expanded ex vivo into aggressive cytotoxic effector cells (CEC) comprising T, NK and NKT cells. We identified the phenotype, cytotoxicity and mechanisms of killing of these CEC. METHODS: CY- and G-CSF-mobilized PBMC from myeloma patients were placed in Aim-V serum-free medium, IL-2 (50 IU/mL) and OKT-3 (50 ng/mL). Cytotoxicity was evaluated by selectively blocking the TCR, MHC class I or NKG2D receptor. RESULTS: The CEC expanded three-fold by day 7 and aggressively lysed myeloma cells (41.9%) compared with day 0 (4%; P=0.012). CD8+ CD56+ NKT cells performed the majority of lysis. The CD8+ cells greatly increased NKG2D expression during culture (P=0.005). Cytotoxicity correlated with target NKG2D ligand expression (P=0.0002). Blocking the TCR or MHC class I did not affect cytotoxicity (P>0.22). CD8+ cell-mediated lysis dropped 48% when the NKG2D receptor was blocked. Day 7 CEC aggressively lysed myeloma cells in an MHC- and non-MHC-restricted fashion, through the NKG2D receptor. DISCUSSION: Because MHC expression is often down-regulated on tumor cells and the NKG2D ligands are generally specific to malignant cells, the adoptive transfer of CEC that kill through different pathways may circumvent tumor-resistant mechanisms and improve outcomes.

CD8 Antigens↗
PubMed2005

Quality-adjusted survival in a crossover trial of letrozole versus tamoxifen in postmenopausal women with advanced breast cancer.

BACKGROUND: Results from a phase III study of postmenopausal women with advanced breast cancer demonstrated longer time to disease progression for patients taking letrozole versus tamoxifen. This analysis compares the trade-offs between progression-free survival and toxicity. DESIGN: Quality-adjusted survival was calculated using Q-TWiST (quality-adjusted time without symptoms or toxicity). Survival curves were partitioned into three health states: toxicity (TOX), disease progression (PROG) and periods without toxicity or disease progression (TWiST). The utility-weighted sum of the health state durations was derived and compared. RESULTS: There was not a significant difference in mean duration of serious adverse events prior to progression between the letrozole (n=453) and tamoxifen (n=454) groups (2.2 and 2 months, respectively). For TWiST, the mean duration for letrozole was 11.5 months, versus 8.5 months for tamoxifen (P <0.001). The mean duration of PROG was 11.5 months for letrozole and 12.7 months for tamoxifen (P=0.047). Using utility weights of 0.5 for TOX and PROG resulted in a 2.5-month difference in quality-adjusted survival favoring letrozole (P <0.0001). CONCLUSIONS: The longer time to disease progression with letrozole versus tamoxifen was achieved without increased time with adverse events and resulted in more quality-adjusted survival for patients on letrozole.

Aged↗
PubMed2004

Modafinil for the treatment of pain-associated fatigue: review and case report.

Fatigue is a symptom that is frequently found in chronic pain patients with low back pain and/or neck pain. At the present time, no specific psychopharmacological treatment for this problem has been identified. Modafinil is a wakefulness-promoting agent that the FDA has approved for the treatment of excessive daytime sleepiness associated with narcolepsy. There have been reports on the use of modafinil for the treatment of fatigue in various neurological syndromes. This literature is reviewed. As such, modafinil treatment was initiated for a patient with severe fatigue associated with chronic low back pain and neck pain. There was dramatic improvement in fatigue and associated function. This case is described. It is the first such case report in the literature. The significance of this finding to the treatment of pain-associated fatigue is discussed.

Adult↗
PubMed2003

Near-threshold production of the multistrange Xi- hyperon.

The yield for the multistrange Xi(-) hyperon has been measured in 6A GeV Au+Au collisions via reconstruction of its decay products pi(-) and Lambda, the latter also being reconstructed from its daughter tracks of pi(-) and p. The measurement is rather close to the threshold for Xi(-) production and therefore provides an important test of model predictions. The measured yield for Xi(-) and Lambda are compared for several centralities. In central collisions the Xi(-) yield is found to be in excellent agreement with statistical and transport model predictions, suggesting that multistrange hadron production approaches chemical equilibrium in high baryon density nuclear matter.

Journal Article↗
PubMed2003

Comparison of source images for protons, pi-'s, and lambda's in 6A GeV Au+Au collisions.

Source images are extracted from two-particle correlations constructed from strange and nonstrange hadrons produced in 6A GeV Au+Au collisions. Very different source images result from pp vs p Lambda vs pi(-)pi(-) correlations. Scaling by transverse mass can describe the apparent source size ratio for p/pi(-) but not for Lambda/pi(-) or Lambda/p. These observations suggest important differences in the space-time emission histories for protons, pions, and neutral strange baryons produced in the same events.

Journal Article↗
PubMed2002

Longitudinal flow of protons from (2-8)A GeV central Au+Au collisions.

Rapidity distributions of protons from central 197Au+197Au collisions measured by the E895 Collaboration in the energy range from (2-8)A GeV at the Brookhaven AGS are presented. Longitudinal flow parameters derived using a thermal model including collective longitudinal expansion are extracted from these distributions. The results show an approximately linear increase in the longitudinal flow velocity, (L), as a function of the logarithm of beam energy.

Journal Article↗
PubMed2001

Model-independent source imaging using two-pion correlations in (2 to 8)a GeV Au+Au collisions.

We report a particle source imaging analysis based on two-pion correlations in high multiplicity Au+Au collisions at beam energies between 2A and 8A GeV. We apply the imaging technique introduced by Brown and Danielewicz, which allows a model-independent extraction of source functions with useful accuracy out to relative pion separations of about 20 fm. The extracted source functions have Gaussian shapes. Values of source functions at zero separation are almost constant across the energy range under study. Imaging results are found to be consistent with conventional source parameters obtained from a multidimensional Hanburg-Brown-Twiss analysis.

Journal Article↗
PubMed2001

The influence of two different dental local anaesthetic solutions on the haemodynamic responses of children undergoing restorative dentistry: a randomised, single-blind, split-mouth study.

OBJECTIVES: This investigation was designed to study the haemodynamic effects of two different local anaesthetic solutions during restorative dental treatment in children. DESIGN: A randomised, single-blind, split-mouth cross-over design was employed using children undergoing bilaterally similar restorative treatments over two visits. SETTING: The study was performed in a dental hospital paediatric dentistry department. METHODS: Ten children participated. At one visit the local anaesthetic was 2% lidocaine (lignocaine) with 1:80,000 epinephrine (adrenaline); at the other the anaesthetic was 3% prilocaine with 0.03IU/ml felypressin. Local anaesthetic was administered at a dose of 0.5 ml/10 kg body weight. Blood pressure and heart rate were measured before and during treatment with an automatic blood pressure recorder. Data were analysed by ANOVA and Student's paired t test. RESULTS: Significant differences between treatments in diastolic blood pressure (F = 2.37; P = 0.05) and heart rate (F = 2.98; P< 0.02) were noted. The heart rate increased ten minutes following the injection of the epinephrine-containing solution. The diastolic blood pressure fell 20 minutes after injection of lidocaine with epinephrine. CONCLUSION: The choice of local anaesthetic solution influences the haemodynamic response during restorative treatment in children.

Analysis of Variance↗
PubMed2001

Directed flow of lambda hyperons in (2-6 )A GeV Au+Au collisions.

Directed flow measurements for Lambda hyperons are presented and compared to those for protons produced in the same Au+Au collisions (2A, 4A, and 6A GeV; b<5-6 fm). The measurements indicate that Lambda hyperons flow consistently in the same direction but with smaller magnitudes. A strong positive flow [for Lambdas] has been predicted in calculations which include the influence of the Lambda-nucleon potential. The experimental flow ratio Lambda/p is in qualitative agreement with expectations (approximately 2/3) from the quark counting rule at 2A GeV but is found to decrease with increasing beam energy.

Journal Article↗
PubMed2001

Identifying patients at risk for loss to follow-up after pain center treatment.

OBJECTIVE: This study was designed to identify, at admission to a pain treatment facility, characteristics of patients who will be lost to follow-up after treatment completion. METHOD: Patients were divided into 3 groups depending on how they responded to the 12-month follow-up. The analysis was a between-subjects design using prospective data collected at a comprehensive pain treatment facility. Low back pain patients (n = 168) received 4 weeks of multidisciplinary pain treatment. The main outcome measure was response/nonresponse to follow-up questionnaires. RESULTS: showed that patients who were later lost to follow-up, or who were reluctant to answer follow-ups, could be predicted at treatment admission by measures of pain and functioning. The prediction equation was validated by a second group of patients, treatment noncompleters (n = 55). CONCLUSION: Chronic pain patients who are more likely to be lost to follow-up can be identified upon admission to a pain facility. Procedures that should decrease follow-up attrition could be implemented at program admission.

Journal Article↗
PubMed2001

International Headache Society headache diagnostic patterns in pain facility patients.

OBJECTIVE: Previous studies have indicated that many patients with chronic pain (PWCP) referred to pain facilities for the treatment of neck and/or low back pain complain of associated headaches. The purpose of this study was to characterize the nature of these headaches according to International Headache Society (IHS) headache diagnostic criteria. DESIGN: In preparation for this study, a questionnaire that reflected IHS headache diagnostic criteria was developed. All consecutive patients admitted to our pain facility complaining of headache completed this questionnaire and received a physical and neurologic examination focused on key aspects of headache. A headache interview was also conducted, using the questionnaire as a question guide. All questionnaires were entered in a computerized database, and IHS diagnoses were arrived at for each patient. As many IHS diagnoses as possible were assigned to each PWCP as long as IHS criteria were fulfilled. In addition, a frequency distribution for headache precipitants and neck-associated symptoms was developed and evaluated by discriminant analysis to determine the diagnostic value of these factors in relation to each IHS diagnostic group. SETTING: Pain facility (multidisciplinary pain center). PATIENTS: Consecutive PWCP. RESULTS: Of 1,466 PWCP, 154 (10.5%) were identified as suffering from severe headache interfering with function. Of these, 55.8% indicated that their headaches were related to an injury for which they were seeking treatment and 83.7% had neck pain. Migraine headache represented the most common diagnostic group (90.3%), with cervicogenic headache representing the second most common (33.8%). Of the total group, 44.2% had more than one headache diagnosis, that is, there was overlap. Cervicogenic headache patients had the greatest percentage of overlap (94.2%), with migraine patients being second (68.3%). The most frequent headache precipitant was mental stress, followed by neck position and activity/exercise. The migraine and cervicogenic headache groups had a statistically significant greater number of neck-associated symptoms when compared with the remaining patients. Of the total headache group, 74.6% complained that they had a tender point at the back of their neck. Cervicogenic, migraine, and tension PWCP had the greatest frequency of head or neck tender points. The discriminant analysis for neck-associated symptoms yielded the following symptoms as the most common predictors of headache across IHS diagnostic groups: clues to onset were severe headache beginning at the neck or tender point and numbness in arms and legs; headache brought on by neck position and arms overhead; and neck symptoms consisting of a tender point in the neck and feeling severe headache in the neck. CONCLUSIONS: Headache can and should be considered a frequent comorbid condition in PWCP. Because of the overlap data, more precise diagnostic criteria may be required to separate cervicogenic headache from migraine headache. Neck-associated symptoms seem to be important even to those PWCP diagnosed with migraine headache.

Headache↗
PubMed2000

Antiflow of K(0)(s) mesons in 6A GeV Au + Au collisions

We have measured the sideward flow of neutral strange ( K(0)(s)) mesons in 6A GeV Au+Au collisions. A prominent antiflow signal is observed for an impact parameter range ( b less, similar7 fm) which spans central and midcentral events. Since the K(0)(s) scattering cross section is relatively small in nuclear matter, this observation suggests that the in-medium kaon vector potential plays an important role in high density nuclear matter.

Journal Article↗
PubMed2000

Sideward flow in Au+Au collisions between 2A and 8A GeV

Using the large acceptance Time Projection Chamber of experiment E895 at Brookhaven, measurements of collective sideward flow in Au+Au collisions at beam energies of 2A, 4A, 6A, and 8A GeV are presented in the form of in-plane transverse momentum and the first Fourier coefficient of azimuthal anisotropy v(1). These measurements indicate a smooth variation of sideward flow as a function of beam energy. The data are compared with four nuclear transport models which have an orientation towards this energy range. All four exhibit some qualitative trends similar to those found in the data, although none show a consistent pattern of agreement within experimental uncertainties.

Journal Article↗
PubMed2000

Bombarding energy dependence of pi(-) interferometry at the brookhaven AGS

We present the first excitation function of pi(-) intensity interferometry at Alternating Gradient Synchrotron (AGS) energies (2-8 A GeV). The sensitivity of the multidimensional correlation functions to the geometry and dynamics of the pion-emitting system provides a stringent test of transport models of heavy ion collisions. Detailed comparisons with a realistic transport model, both with and without an explicit nuclear mean field, suggest that the beam energy evolution in the reaction dynamics is different in the model than in the data. A significantly increased pi(-) emission time scale, which has been suggested as a signal of the onset of the transition to quark-gluon plasma, is not observed.

Journal Article↗
PubMed2000

Variance and sample size calculations in quality-of-life--adjusted survival analysis (Q-TWiST).

The Quality-Adjusted Time Without Symptoms or Toxicity (Q-TWiST) statistic previously introduced by Glasziou, Simes and Gelber (1990, Statistics in Medicine 9, 1259-1276) combines toxicity, disease-free survival, and overall survival information in assessing the impact of treatments on the lives of patients. This methodology has received positive reviews from clinicians as intuitive and useful, but to date, the variance of this statistic has remained unspecified. We review aspects of the Q-TWiST method for analyzing clinical trial data, extend the method to accommodate multiple treatment arms, and provide closed-form asymptotic variance formulas. We also provide a framework for designing Q-TWiST clinical trials with sample sizes determined using the derived asymptotic variance formulas. Trials currently collecting quality of life data did not have the benefit of these sample size calculation techniques in designing their studies.

Biometry↗
PubMed2000

Anti-MAM antibodies in rheumatic disease: evidence for a MAM-like superantigen in rheumatoid arthritis?

OBJECTIVE: Superantigens (SAg) are potent immunomodulatory microbial proteins that can activate T cells, B cells, natural killer cells, and monocytes and are known to trigger experimental autoimmune disease. We investigated whether sera from patients with rheumatic diseases contained elevated antibodies to Mycoplasma arthritidis mitogen (MAM) or staphylococcal enterotoxins A and B (SEA and SEB). METHODS: Standard ELISA were used to measure IgG responses to SAg and IgM and IgG rheumatoid factors and total IgM and IgG levels. Modifications of standard lymphocyte proliferation assays were used to determine functional consequences of the observed antibodies. RESULTS: Antibodies to MAM were elevated in sera from patients with rheumatoid arthritis (RA) compared to sera from patients with systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome, or healthy controls. Responses to other SAg were also elevated in rheumatic disease sera, but the levels were not specific for a given rheumatic disease. Anti-superantigen antibody levels did not correlate with the presence of rheumatoid factor. CONCLUSION: The selected elevation of antibodies to MAM in RA sera suggests that MAM or a MAM-like molecule might be associated with RA, whereas elevation of antibodies to SEA and SEB in sera from patients with rheumatic diseases was less specific.

Antibodies↗
PubMed1999

Immunotherapy of mice with an irradiated melanoma vaccine coupled with interleukin-12.

Interleukin (IL)-12 can activate cytotoxic lymphocytes, stimulate natural killer cell activity, induce the production of INF-gamma and inhibit the development of various experimental tumors. We previously demonstrated that immunotherapy of melanoma bearing mice with an irradiated melanoma vaccine (IMV) coupled with IL-2 or GM-CSF had beneficial effects against primary melanoma growth and against subsequent spontaneous metastasis. We also had found that treatment of melanoma bearing mice with IL-12 (300 ng/day) for 4 weeks inhibited the development of primary melanoma tumors in 40% of mice. The purpose of this study was to investigate the efficacy of combined therapy of experimental melanoma with an IMV prepared from B16F10 melanoma cells coupled with IL-12 treatment. C57BL/6 mice were challenged subcutaneously in the tail with B16F10 melanoma cells and by the 45th day, more than 50% of the mice had developed visible primary melanoma tumors at the injection site. Subsequent immunotherapy of mice with IMV, when coupled with IL-12, provided partial inhibition of primary melanoma tumor growth. Optimal results against primary tumor growth were observed when IMV therapy was coupled with IL-12 at a dose of 50 ng/day. Combination of IMV with IL-12 at a dose of 100 ng/day significantly reduced melanoma metastasis to the lungs compared with control mice, and an improvement in mean survival time was observed in mice treated with a combination of IMV with IL-12 (300 ng/day).

Animals↗