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Biomedical subjects

D Barton

Publications and source records attributed to D Barton.

At least 19 recordsLinked to original sources
PubMed2004

A phase I trial of idiotypic vaccination with HMFG1 in ovarian cancer.

INTRODUCTION: An extended phase I trial was conducted in a total of 26 patients with ovarian cancer. The objectives were to assess the safety and tolerability of idiotypic vaccination using the murine monoclonal antibody HMFG1 (anti-MUC1), and to develop robust assays to monitor humoral immune responses generated against either the antibody or MUC1. MATERIAL AND METHODS: All patients had undergone standard debulking surgery (where appropriate) and at least one regimen of platinum-based chemotherapy. Eligibility criteria included: (a) residual disease at the end of chemotherapy, (b) relapsed disease, and (c) pathologically confirmed second complete remission following salvage chemotherapy. Patients received a priming dose of 25 mg of HMFG1 either intravenously or intraperitoneally, followed by up to six intradermal doses of HMFG1 in 10% Alhydrogel at intervals of 1 month. The three dose levels were 0.5 mg, 1 mg and 5 mg. We devised modifications of published protocols for the measurement of anti-idiotypic and anti-MUC1 antibody responses and also extended the use of the IAsys resonant mirror biosensor to measure the kinetics of the idiotypic network response in these patients. RESULTS: There were no serious adverse events at any dose level. The trial confirmed that all doses could be administered safely with minimal toxicity. No clinical responses were seen in patients with evaluable disease. ELISA for anti-idiotypic antibodies (Ab2) showed significant levels in patients who completed the protocol. There were no significant differences in the levels of Ab2 generated by the different doses of antibody. These results were confirmed by biosensor assays for Ab2, which also showed affinity maturation of the Ab2 response as patients progressed through the vaccination protocol. Biosensor assays also demonstrated no difference in the affinity of Ab2 generated by different booster doses of HMFG1. ELISA for anti-MUC1 antibodies showed less consistent results, with very small but statistically significant rises in anti-MUC1 signals seen in 38% of patients who completed the vaccination regimen. DISCUSSION: The clinical endpoints of safety and tolerability were met. The assays developed for this project have shown reproducibility and may provide surrogate endpoints to assess vaccination for future trials. The use of similar biosensors may be of particular relevance for monitoring of humoral immune responses in other vaccine trials. The low levels of anti-MUC1 antibodies generated may correspond with the lack of clinical efficacy in the few patients with evaluable disease.

Antibodies, Anti-Idiotypic↗
PubMed2004

Recombinant GH replacement in hypopituitary adults improves endothelial cell function and reduces calculated absolute and relative coronary risk.

OBJECTIVE: Adult GH deficiency (GHD) is linked to endothelial dysfunction and vascular disease. We examined the effect of 12 months of GH therapy on endothelial function, C-reactive protein (CRP) and coronary risk. DESIGN: Open-design intervention study. PATIENTS: Fourteen GH-deficient patients (nonsmokers, without diabetes, hypertension or vascular disease) studied before, 6 months and 12 months after GH therapy. MEASUREMENTS: Flow-mediated dilatation (FMD), carotid intima-media thickness (IMT) thrombomodulin (TM), E-selectin, CRP, lipid profile, blood pressure and anthropometric data were recorded. We used the Framingham equation to calculate coronary risk. RESULTS: FMD improved (7.5 +/- 1.62 vs. 11.93 +/- 1.52, P = 0.038). Overall there was no change in IMT, TM, E-selectin or CRP. The correlation between TM and FMD showed a trend for statistical significance (r = -0.54, P = 0.056). Changes in CRP correlated with change in IGF-1 (r = -0.67, P = 0.012); E-selectin correlated with high density lipoprotein (HDL)-cholesterol (r = -0.60, P = 0.028), triglycerides (r = 0.68, P = 0.01) and waist-to-hip ratio (WHR) (r = 0.71, P = 0.006). Systolic (127.36 +/- 4.47 vs. 120.36 +/- 3.50, P = 0.017) and diastolic (84.71 +/- 2.73 vs. 76.93 +/- 2.03, P = 0.005) blood pressure decreased. HDL-cholesterol increased (0.70 +/- 0.05 vs. 0.93 +/- 0.06, P = 0.001). WHR decreased (0.90 +/- 0.02 to 0.88 +/- 0.02, P = 0.043) without changes in weight or body mass index (BMI). Ten-year absolute (P = 0.009) and relative (P = 0.002) cardiac risk decreased. CONCLUSION: Biophysical test of endothelial function (FMD) improved after 12 months of GH therapy but there was no significant change in biochemical endothelial or inflammatory markers. Calculated coronary risk decreased mainly due to reduction in systolic and diastolic blood pressure and increase in HDL-cholesterol.

Adult↗
PubMed2003

n-p short-range correlations from (p,2p+n) measurements.

We studied the 12C(p,2p+n) reaction at beam momenta of 5.9, 8.0, and 9.0 GeV/c. For quasielastic (p,2p) events p(f), the momentum of the knocked-out proton before the reaction, was compared (event by event) with p(n), the coincident neutron momentum. For |p(n)|>k(F)=0.220 GeV/c (the Fermi momentum) a strong back-to-back directional correlation between p(f) and p(n) was observed, indicative of short-range n-p correlations. From p(n) and p(f) we constructed the distributions of c.m. and relative motion in the longitudinal direction for correlated pairs. We also determined that 49+/-13% of events with |p(f)|>k(F) had directionally correlated neutrons with |p(n)|>k(F).

Journal Article↗
PubMed2003

Importance of combined-modality therapy for primary bone lymphoma.

Primary bone lymphoma (PBL) is a rare entity and comprises about 5% of all extranodal non-Hodgkin's lymphomas (NHL) and 7% of all primary bone tumors. To date there is no consensus about the optimal treatment for PBL. We retrospectively reviewed all cases of PBL treated at Hospital São Paulo, Brazil, over a 10-year-period (January 1992-January 2002). Medical records of 7 patients with PBL were reviewed and information on age at diagnosis, sex, NHL clinical staging (CS), treatment and response to treatment were retrieved. Five patients (72%) received combined-modality therapy (CMT) and all of them are in complete remission (CR) with a median follow up of 19 months (ranging from 12 to 144 months). We conclude that PBL is a potentially curable malignancy and treatment should be undertaken in a multiprofessional approach, in order to provide the best support which probably has to include chemotherapy, radiotherapy and, for patients with IPI higher than 2, consolidation with stem-cell transplantation.

Adult↗
PubMed2002

Single-strand conformation polymorphism-based analysis reveals genetic variation within Spirometra erinacei (Cestoda: Pseudophyllidea) from Australia.

This study examined genetic variability within Spirometra erinacei (Cestoda: Pseudophyllidea) from different host species and geographical origins in Australia using a polymerase chain reaction (PCR)-based mutation detection approach, followed by DNA sequencing. Part of the cytochrome c oxidase subunit 1 gene (p cox 1) was amplified by PCR, scanned for sequence variation by single-strand conformation polymorphism (SSCP), and representative samples from different host species were selected for DNA sequencing. While no variation in SSCP profiles was detected among S. erinacei samples from dog, fox, cat, tiger snake and python, they differed in profile from 5 specimens from the green tree frog (Litoria caerulea). This was supported by sequence data which demonstrated that p cox 1 sequences of samples from the latter host species differed at 8 of 393 (2%) nucleotide positions from those from the non-amphibian host. Using a nucleotide difference in the p cox 1 sequence, a PCR-linked restriction fragment length polymorphism (RFLP) could be employed to unequivocally delineate between samples from non-amphibian and amphibian hosts. These findings demonstrate the existence of at least two genotypes within S. erinacei, which may have important implications for studying the epidemiology, ecology and systematics of this cestode.

Animals↗
PubMed2001

Energy dependence of nuclear transparency in C (p,2p) scattering.

The transparency of carbon for (p,2p) quasielastic events was measured at beam momenta ranging from 5.9 to 14.5 GeV/c at 90 degrees c.m. The four-momentum transfer squared (Q2) ranged from 4.7 to 12.7 (GeV/c)(2). We present the observed beam momentum dependence of the ratio of the carbon to hydrogen cross sections. We also apply a model for the nuclear momentum distribution of carbon to obtain the nuclear transparency. We find a sharp rise in transparency as the beam momentum is increased to 9 GeV/c and a reduction to approximately the Glauber level at higher energies.

Journal Article↗
PubMed2001

Redefining leadership responsibilities following organizational redesign.

A redefinition of leadership roles was necessitated by the adoption of program management, which accompanied the merger of two large academic hospitals, each of which consisted of two sites. Directors of professional departments were removed when staff were deployed to programs. Program directors were selected to manage the new programs, and profession leaders were identified to monitor standards of practice. The roles and accountabilities of the new program and profession leaders needed to be clarified for incumbents and other hospital staff. This article describes the process undertaken to clarify those responsibilities. The resulting Guide outlines 14 specific and collaborative responsibilities of program and profession leaders. Plans for review and future development of the Guide are discussed.

Guidelines as Topic↗
PubMed2001

Hot flashes: aetiology and management.

Menopause, an event often accompanied by symptoms such as hot flashes, can have a significant impact on a woman's quality of life. A majority of women will experience hot flashes at some point in their life, given a normal life span. Despite multiple theories, the exact pathophysiology of hot flashes is not yet known. Many types of treatment options exist for women with hot flashes, from hormonal and nonhormonal pharmacological therapies to nonpharmacological interventions. Choosing the best treatment option for specific women involves knowledge of the risks and benefits of each treatment. Hormones (estrogen and/or progesterone, or tibolone alone) are still the most effective option available, resulting in an 80 to 90% reduction in hot flashes. The best nonhormonal treatment to date is in the class of newer antidepressants that comprises various selective reuptake inhibitors; for example, venlafaxine provides about a 60% reduction in hot flashes. This article provides evidence-based information about available treatment options for hot flash management, with special consideration of populations such as breast cancer survivors.

Estrogens↗
PubMed2001

Measuring quality of care with an inpatient elderly population. The geriatric resource nurse model.

Nurses provide health services to an increasing number of older adults in acute care settings. Acute care nurses are committed to giving patients the highest quality care while recognizing the importance of delivering care in a cost-effective manner. In this study, a unit-based, nurse-centered geriatric program is evaluated. The program is designed to enhance the knowledge and skill of staff nurses in providing care to elderly patients. Both quantitative and qualitative methods are used to assess geriatric resource nurses' (GRNs) influence on quality and cost outcomes of the elderly participants. Patients age 65 years and older were randomly selected from two general medical units of a major academic tertiary care center in the southeastern United States. Data were collected during an 18-month period in 1996 and 1997. A total of 129 participants provided data for quantitative analysis. A subset of 34 participants (17 from the unit where GRNs were on staff and 17 from a control unit) was interviewed about their experience during hospitalization. This information was analyzed for common themes and trends using appropriate qualitative techniques. Demographic variables and common measures of illness severity and complexity showed comparable patient populations on the two units. However, results of quantitative analyses indicated significant differences between groups on admission for several of the health status measures. Participants on the unit without GRNs were found to have more problems with pain, incontinence, and mobility. Administrative measures showed the number of patients readmitted to the hospital within 31 days of discharge and the length of stay associated with this initial readmission were significantly lower on the unit with GRNs. The use of vest-type physical restraints was also less frequent on this unit. Elderly patients in both groups indicated they have special needs related to normal aging changes and chronic illnesses, resulting in higher levels of fragility and decreased energy reserves. They identified specific functional areas for which help was needed. These include assistance with bathing, eating, sleeping, mobility, and elimination. Fewer participants on the intervention unit reported decline in activities of daily living (ADL) function during hospitalization than did control participants. Participants in both groups stressed the importance of nurses' demonstrating understanding and caring when working with older individuals.

Aged↗
PubMed2000

Mice lacking the transcription factor RelB develop T cell-dependent skin lesions similar to human atopic dermatitis.

Mice with a targeted disruption of the Rel / NF-kappaB family member RelB develop a complex inflammatory phenotype and hematopoietic abnormalities. RelB-deficient (relB(- / -)) mice were clinically normal until 4 - 10 weeks after birth when thickening of the skin and hair loss developed. Histological and immunohistochemical evaluation of relB(- / -) skin lesions revealed hyperkeratosis and marked epidermal hyperplasia. Many CD4(+) T cells and eosinophils mixed with lesser numbers of CD8(+) T cells and neutrophils were present in the dermis. There was a moderate increase of MHC class II-positive dermal dendritic cells and dermal mast cells. Increased expression of Th2 cytokines correlated with increased mRNA levels of eotaxin and CCR3 in relB(- / -) skin. The dermatitis did not develop in the offspring of relB(- / -) mice crossed with transgenic mice that lack peripheral T cells, demonstrating that the skin lesions were T cell dependent. The dermatitis observed in RelB-deficient mice had many similarities with atopic dermatitis in human patients including infiltrating CD4(+) T cells and eosinophils in the skin, increased number of eosinophils in the blood and increased serum IgE. Thus, the relB(- / -) mouse should be a useful model to study the pathogenesis of this common allergic human disease.

Animals↗
PubMed2000

Combining platinum, paclitaxel and anthracycline in patients with advanced gynaecological malignancy.

Two meta-analyses have suggested that the addition of an anthracycline to platinum-based chemotherapy may improve survival in advanced ovarian cancer, and two randomised trials have demonstrated superiority of paclitaxel over cyclophosphamide in platinum combinations. A combination of platinum, anthracycline and paclitaxel would, therefore, be a reasonable experimental arm of any future randomised trial in patients with epithelial ovarian carcinoma (EOC). Patients who required chemotherapy for EOC but were ineligible for standard trials or had other gynaecological tumours that required similar platinum-based chemotherapy were considered for this pilot. The platinum/anthracycline/paclitaxel regimen (G-CAT) was given 3-weekly and consisted of doxorubicin 50 mg/m(2) or epirubicin 60 mg/m(2) intravenously (i.v.) bolus, paclitaxel 175 mg/m(2) (i.v.) over 3 h and either cisplatin 75 mg/m(2) (i.v.) or carboplatin AUC 6, with granulocyte colony-stimulating factor (G-CSF) at the neutrophil nadir. Different combinations were used in order to determine the least toxic regimen. Toxicity and response were assessed according to CTC and WHO criteria, respectively. 26 patients entered the study, 13 with EOC and 13 with other gynaecological cancers (peritoneal, fallopian tube, mixed Mullerian). Median age was 49 years (range: 27-67). 8 patients received carboplatin/doxorubicin/paclitaxel, 8 cisplatin/doxorubicin/paclitaxel and 10 carboplatin/epirubicin/paclitaxel. A total of 135 cycles of chemotherapy were delivered, with a median of 6 cycles per patient (range: 2-6). 54 (40%) cycles required G-CSF support and 17 (65%) patients required at least one dose reduction. All patients experienced grade 4 neutropenia and 13 (50%) patients developed grade 3-4 thrombocytopenia (12 of whom had received carboplatin). There were 4 (15%) patients with grade 3/4 infections but no septic deaths. Non-haematological toxicities were manageable, lethargy occurred in 75% of cisplatin-treated patients. Grade 1/2 cardiotoxicity, as assessed pre- and post-treatment by left ventricular ejection fraction, was observed in 6/13 (46%) patients who had received doxorubicin and 2/7 (29%) epirubicin-treated patients. No clinically detectable cardiac toxicity was encountered. The response rate in 25 evaluable patients was 76% (12 CR, 7 PR). Dose intensity was highest in the carboplatin/epirubicin/paclitaxel combination. G-CAT shows high activity and can be administered safely, but only very fit patients are suitable for this regimen as it is associated with considerable toxicity. Carboplatin/epirubicin/paclitaxel was the best tolerated regimen overall.

Adult↗
PubMed2000

Psychosocial aspects of sexual disorders.

BACKGROUND: The sexual urge is as old as humanity itself and necessary for the propagation of all species. However, sexuality is not only influenced by the integrity of the genital tract, but also the limbic system and spinal arousal centres. Social and cultural influences on sexual behaviour are in a continuous process of change. OBJECTIVE: This article attempts to highlight the importance of a multifaceted systemic approach to a common and distressing problem. DISCUSSION: The aetiology of sexual dysfunction is diverse and usually results from a complex interaction of biological, psychological and social factors. Consequently, there is little to be gained from trying to determine whether a disorder is either biological or psychological, as both will be relevant to a certain extent in every case. Even in a case with a clear biological cause (e.g. diabetic neuropathy) the treatment and long term consequences of the secondary sexual disorder will be affected by psychosocial implications. Sexual functioning can be strongly influenced by one's own sense of self and social competence.

Adult↗
PubMed2000

Taking a sexual history.

BACKGROUND: Significant social changes have resulted in increased exposure to sexual issues and greater tolerance of sexual behaviours such as premarital sex and homosexuality. These changes are not universal, however. We live in a multicultural society with widely varying sexual mores and frequent clashes of culture across generations. The media has contributed to unrealistic expectations about body image and sexual performance while at the same time increasing awareness of sexually transmitted diseases. Consequently, patients seek help with these issues and will discuss them freely if the general practitioner is comfortable in the area of sexual health. OBJECTIVE: This article outlines an approach to sexual assessment and ways of addressing the barriers faced in taking a sexual history. DISCUSSION: All sexual disorders involve biological, psychological and social factors. General practice can provide a safe, non-judgmental environment for the patient to divulge sexual difficulties and have these dealt with holistically. However, this takes time, a significant obstacle in current practice.

Australia↗
PubMed1999

A symposium on psychotherapy in the age of managed care.

This article is based upon a symposium presented at Vanderbilt University Medical Center on the Department of Psychiatry's 50th anniversary (September 20, 1997). The panel of psychotherapy scholar-clinicians discusses issues including: whether or not managed care and psychotherapy are compatible; the relevance of the Consumer Reports' psychotherapy study to MCOs' emphasis on brief therapy; how MCOs impact upon the therapist-patient relationship; the effects of MCOs on the psychotherapist's personal and professional identity; and training psychotherapists in the era of managed care. The paper is dedicated to Pietro Castelnuovo-Tedesco, M.D., Vanderbilt's Blakemore Professor of Psychiatry, who died on January 24, 1998.

Humans↗