PubMed Health⌕ Search

Biomedical subjects

Elizabeth Jones

Publications and source records attributed to Elizabeth Jones.

15 recordsLinked to original sources
PubMed2006

Routine interval computed tomography to detect new soft-tissue disease might be unnecessary in patients with androgen-independent prostate cancer and metastasis only to bone.

OBJECTIVE: To identify patients with androgen-independent prostate cancer (AIPC) with bone metastasis and no soft-tissue metastases at the time of protocol enrollment, and analyse their disease progression by computed tomography (CT), bone scan, and prostate-specific antigen (PSA) level to determine the utility of routine interval CT in such patients. PATIENTS AND METHODS: Bone is the most common metastatic site in patients with AIPC and the only site of metastatic disease for many; because some with initial bone metastasis eventually develop soft-tissue disease, many clinical trials use routine CT to monitor for the latter as a sign of disease progression, but the actual incidence of new soft-tissue metastases is unknown and the role of routine interval CT in monitoring for disease progression, especially for asymptomatic patients, is unclear. Thus we reviewed 175 cases of metastatic AIPC from three randomized phase II clinical trials (docetaxel/thalidomide, docetaxel/vaccine, and ketoconazole/alendronate) at the National Cancer Institute between 1995 and 2004. The patients' PSA levels were assessed every 4 weeks, and CT and bone scans were done every 2-3 months. We retrospectively identified patients with bone metastasis only and examined subsequent CT for the occurrence of soft-tissue disease. For patients with progressive disease, we also examined bone scan and PSA progression. RESULTS: Of 175 patients with metastatic prostate cancer, 105 (60%) had bone metastasis only, 12 (6.9%) had soft-tissue metastases only, and 58 (33.1%) had both bone and soft-tissue metastases. The median (range) follow-up was 8 (1-44) months for the 105 patients with bone metastasis only. During that time, two patients (1.9%) developed new soft-tissue disease; one developed right iliac fossa lymphadenopathy after 8 months and the other developed a perirectal mass after 12 months. The patient with new lymphadenopathy also had multiple new bone lesions identified by bone scan and PSA progression. The patient with the perirectal mass had PSA progression and a palpable abnormality. CONCLUSION: This review of patients with AIPC and bone metastasis only, followed for a median of 8 months on clinical trials, shows that the incidence of asymptomatic new soft-tissue disease as the only sign of disease progression is quite low. Therefore, routine CT to exclude new soft-tissue disease in this population appears to be unwarranted. We recommend that for these patients CT is done only at the time of disease progression, as shown by bone scan, PSA level, or clinical presentation. We do not exclude the possibility that patients who remain on trial for significantly longer periods might benefit from routine interval CT.

Adult↗
PubMed2006

A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer.

PURPOSE: Docetaxel has activity against androgen-independent prostate cancer and preclinical studies have shown that taxane-based chemotherapy can enhance antitumor response of vaccines. The primary objective of this study was to determine if concurrent docetaxel (with dexamethasone) had any effect on generating an immune response to the vaccine. Secondary end points were whether vaccine could be given safely with docetaxel and the clinical outcome of the treatment regimen. EXPERIMENTAL DESIGN: The vaccination regimen was composed of (a) recombinant vaccinia virus (rV) that expresses the prostate-specific antigen gene (rV-PSA) admixed with (b) rV that expresses the B7.1 costimulatory gene (rV-B7.1), and (c) sequential booster vaccinations with recombinant fowlpox virus (rF-) containing the PSA gene (rF-PSA). Patients received granulocyte macrophage colony-stimulating factor with each vaccination. Twenty-eight patients with metastatic androgen-independent prostate cancer were randomized to receive either vaccine and weekly docetaxel or vaccine alone. Patients on the vaccine alone arm were allowed to cross over to receive docetaxel alone at time of disease progression. The ELISPOT assay was used to monitor immune responses for PSA-specific T cells. RESULTS: The median increase in these T-cell precursors to PSA was 3.33-fold in both arms following 3 months of therapy. In addition, immune responses to other prostate cancer-associated tumor antigens were also detected postvaccination. Eleven patients who progressed on vaccine alone crossed over to receive docetaxel at time of progression. Median progression-free survival on docetaxel was 6.1 months after receiving vaccine compared with 3.7 months with the same regimen in a historical control. CONCLUSION: This is the first clinical trial to show that docetaxel can be administered safely with immunotherapy without inhibiting vaccine specific T-cell responses. Furthermore, patients previously vaccinated with an anticancer vaccine may respond longer to docetaxel compared with a historical control of patients receiving docetaxel alone. Larger prospective clinical studies will be required to validate these findings.

Acid Phosphatase↗
PubMed2006

Naïve T-cell dynamics in human immunodeficiency virus type 1 infection: effects of highly active antiretroviral therapy provide insights into the mechanisms of naive T-cell depletion.

Both naïve CD4+ and naïve CD8+ T cells are depleted in individuals with human immunodeficiency virus type 1 (HIV-1) infection by unknown mechanisms. Analysis of their dynamics prior to and after highly active antiretroviral therapy (HAART) could reveal possible mechanisms of depletion. Twenty patients were evaluated with immunophenotyping, intracellular Ki67 staining, T-cell receptor excision circle (TREC) quantitation in sorted CD4 and CD8 cells, and thymic computed tomography scans prior to and approximately 6 and approximately 18 months after initiation of HAART. Naïve T-cell proliferation decreased significantly during the first 6 months of therapy (P < 0.01) followed by a slower decline. Thymic indices did not change significantly over time. At baseline, naïve CD4+ T-cell numbers were lower than naive CD8+ T-cell numbers; after HAART, a greater increase in naïve CD4+ T cells than naïve CD8+ T cells was observed. A greater relative change (n-fold) in the number of TREC+ T cells/mul than in naïve T-cell counts was observed at 6 months for both CD4+ (median relative change [n-fold] of 2.2 and 1.7, respectively; P < 0.01) and CD8+ T cell pools (1.4 and 1.2; P < 0.01). A more pronounced decrease in the proliferation than the disappearance rate of naïve T cells after HAART was observed in a second group of six HIV-1-infected patients studied by in vivo pulse labeling with bromodeoxyuridine. These observations are consistent with a mathematical model where the HIV-1-induced increase in proliferation of naïve T cells is mostly explained by a faster recruitment into memory cells.

Adult↗
PubMed2006

Living in three dimensions: 3D nanostructured environments for cell culture and regenerative medicine.

Research focused on deciphering the biochemical mechanisms that regulate cell proliferation and function has largely depended on the use of tissue culture methods in which cells are grown on two-dimensional (2D) plastic or glass surfaces. However, the flat surface of the tissue culture plate represents a poor topological approximation of the more complex three-dimensional (3D) architecture of the extracellular matrix (ECM) and the basement membrane (BM), a structurally compact form of the ECM. Recent work has provided strong evidence that the highly porous nanotopography that results from the 3D associations of ECM and BM nanofibrils is essential for the reproduction of physiological patterns of cell adherence, cytoskeletal organization, migration, signal transduction, morphogenesis, and differentiation in cell culture. In vitro approximations of these nanostructured surfaces are therefore desirable for more physiologically mimetic model systems to study both normal and abnormal functions of cells, tissues, and organs. In addition, the development of 3D culture environments is imperative to achieve more accurate cell-based assays of drug sensitivity, high-throughput drug discovery assays, and in vivo and ex vivo growth of tissues for applications in regenerative medicine.

Animals↗
PubMed2005

A phase II study of perifosine in androgen independent prostate cancer.

OBJECTIVES: Perifosine is an alkylphospholipid that has exhibited broad antineoplastic activity in preclinical studies. The primary objective of this study was to determine the clinical efficacy of this agent in the treatment of androgen-independent prostate cancer (AIPC) using PSA and clinical criteria. PATIENTS AND METHODS: Nineteen patients with progressive, metastatic AIPC were treated with oral perifosine. Cycles were 28 days in length. A loading dose of 900 mg was given on day 1 of cycle 1 followed by a maintenance dose of 150 mg daily for the next 20 days. A loading dose of 600 mg was administered on the first day of subsequent cycles by the maintenance dose of 150 mg daily for the next 20 days. Pharmacokinetic measurements were made throughout the course of the study. Circulating epithelial cells were collected via leukapheresis on day 0, 3, and 28. RESULTS: Median patient age was 67 years and median PSA was 180 ng/mL (range: 19-904 ng/ml). Grade 1-2 fatigue and gastrointestinal toxicities were common. Pharmacokinetic studies showed an average minimum concentration at steady-state of approximately 4059 ng/ml which correlated well with previous studies. Median time to progression was four weeks. There were no radiographic responses or PSA declines of 50% or greater related to perifosine. CONCLUSIONS: Treatment with perifosine was complicated by fatigue and gastrointestinal toxicity. No significant clinical activity against prostate cancer was observed. This agent does not merit further study in the setting of monotherapy in this population.

Aged↗
PubMed2005

Platypnea-orthodeoxia associated with a fenestrated atrial septal aneurysm: case report.

BACKGROUND: Platypnea-orthodeoxia describes the condition of combined dyspnea and hypoxia respectively, whilst in the upright position, which improves in the recumbent position. CASE REPORT: We present a case of platypnea-orthodeoxia due to a fenestrated atrial septal defect associated with an atrial septal aneurysm. Due to the fenestrated nature of the atrial septal defect, surgical rather than percutaneous correction was performed. CONCLUSION: A high index of suspicion is required to diagnose the syndrome of platypnea-orthodeoxia. Careful echocardiographic evaluation is required to identify the syndrome, and to determine suitability for percutaneous repair.

Aged↗
PubMed2005

A randomized, phase II trial of ketoconazole plus alendronate versus ketoconazole alone in patients with androgen independent prostate cancer and bone metastases.

PURPOSE: Alendronate (AL), a potent oral bisphosphonate, blocks the secretion of matrix metalloproteinase-2 and the establishment of bone metastases in animal models. Ketoconazole (KT) has demonstrated activity in androgen independent prostate cancer (AIPC). In this study we determined whether KT plus AL produced acceptable disease responses compared with KT alone. As the experimental design, 72 patients with progressive AIPC metastatic to bone were randomized to receive KT (1,200 mg daily) plus hydrocortisone (H) (30 mg daily) with or without AL (40 mg daily). Prostate specific antigen (PSA) consensus criteria and radiographic scans were used to determine the proportion of patients with a PSA decrease, time to progression and response duration. The pharmacokinetics of KT and AL were characterized and changes in circulating angiogenic factors were assessed. RESULTS: At a median potential followup of 23.9 months the proportion of patients with a greater than 50% decrease in PSA was similar in the KT/H/AL and KT/H, groups (50% and 47%, respectively). The median duration of response was 8.9 and 6.3 months in the KT/H/AL and KT/H groups, respectively (p = 0.125). Median progression-free survival was not significantly prolonged in the KT/H/AL group (4.6 vs 3.8 months, p = 0.27). There was no significant difference in overall survival between the 2 treatment arms but there was a trend toward improved survival in the KT/H arm (p = 0.074). Toxicity in the 2 groups was mild and there were no clear associations between changes in circulating angiogenic factor levels and clinical outcomes in either treatment arm. CONCLUSIONS: There were no statistically significant differences in response rate, progression-free survival or overall survival between KT/H alone and KT/H plus AL treatment in patients with AIPC. The addition of AL to KT/H may increase the response duration with an acceptable safety profile compared with treatment with KT/H alone. However, the addition of AL offers no survival benefit in patients with AIPC.

Aged↗
PubMed2004

Randomized phase II trial of docetaxel plus thalidomide in androgen-independent prostate cancer.

PURPOSE: Both docetaxel and thalidomide have demonstrated activity in androgen-independent prostate cancer (AIPC). We compared the efficacy of docetaxel to docetaxel plus thalidomide in patients with AIPC. METHODS: Seventy-five patients with chemotherapy-naïve metastatic AIPC were randomly assigned to receive either docetaxel 30 mg/m(2) intravenously every week for 3 consecutive weeks, followed by a 1-week rest period (n = 25); or docetaxel at the same dose and schedule, plus thalidomide 200 mg orally each day (n = 50). Prostate-specific antigen (PSA) consensus criteria and radiographic scans were used to determine the proportion of patients with a PSA decline, and time to progression. RESULTS: After a median potential follow-up time of 26.4 months, the proportion of patients with a greater than 50% decline in PSA was higher in the docetaxel/thalidomide group (53% in the combined group, 37% in docetaxel-alone arm). The median progression-free survival in the docetaxel group was 3.7 months and 5.9 months in the combined group (P =.32). At 18 months, overall survival in the docetaxel group was 42.9% and 68.2% in the combined group. Toxicities in both groups were manageable after administration of prophylactic low-molecular-weight heparin in the combination group. CONCLUSION: In this randomized phase II trial, the addition of thalidomide to docetaxel resulted in an encouraging PSA decline rate and overall median survival rate in patients with metastatic AIPC. After the prophylactic low-molecular-weight heparin was instituted to prevent venous thromboses, the combination regimen was well tolerated. Larger randomized trials are warranted to assess the impact of this combination.

Administration, Oral↗
PubMed2003

A national survey of primary care physicians' colorectal cancer screening recommendations and practices.

BACKGROUND: National data on providers' colorectal cancer (CRC) screening knowledge, attitudes, and practices are sparse. This study assessed primary care physicians' (PCPs') beliefs about the effectiveness of CRC screening, their recommendations for screening, their perceptions of the influence of published guidelines on their CRC screening recommendations, and how they conduct CRC screening in their clinical practices. METHODS: A questionnaire was administered to a nationally representative sample of practicing PCPs. Of 1718 eligible physicians, 1235 (72%) responded. RESULTS: Only 2% of PCPs said they did not recommend CRC screening. Over 80% indicated that they most often recommend CRC screening with fecal occult blood testing and/or flexible sigmoidoscopy, although colonoscopy was perceived as the more effective screening modality. Nearly two-thirds of obstetrician/gynecologists and one-fourth of other practitioners reported conducting fecal occult blood testing exclusively by digital rectal exam. Only 29% of PCPs said they perform sigmoidoscopy. Estimated volumes of ordering, performing, or referring for CRC screening were low, and <20% reported that three-fourths or more of their older patients were up to date with CRC screening as recommended by the physician. Many PCPs reported recommending CRC screening at nonstandard starting ages or too-frequent intervals. CONCLUSIONS: Awareness of CRC screening among PCPs in the United States is high. However, knowledge gaps about the timing and frequency of screening and suboptimal screening delivery were evident.

Adult↗
PubMed2003

Isolation and characterisation of an invertase cDNA from perennial ryegrass (Lolium perenne).

An invertase (LpFT2) cDNA from perennial ryegrass was isolated and sequenced. Nucleotide sequence analysis revealed an ORF of 2016 bp encoding a protein of 671 amino acids. LpFT2 is 76% identical to sugarcane soluble acid invertase, and contains invertase and fructosyltransferase functional domains. LpFT2 is present as a single copy gene and maps to the distal region of LG6 in perennial ryegrass. The expression pattern analysis of LpFT2 revealed transcript accumulation in seedlings and in mature leaf sheaths. The LpFT2 recombinant protein expressed in yeast showed invertase and fructan exohydrolase-like activities with complete breakdown of sucrose, 1-kestose (DP3), 1,1-kestotetraose (DP4) and 1,1,1-kestopentaose (DP5) into glucose and fructose.

Amino Acid Sequence↗
PubMed2002

Colorectal cancer screening with double-contrast barium enema: a national survey of diagnostic radiologists.

OBJECTIVE: This article describes diagnostic radiologists' colorectal cancer screening activities and beliefs about screening effectiveness and future capacity for screening with double-contrast barium enema, and compares radiologists' opinions about colorectal cancer screening with those of primary care physicians. MATERIALS AND METHODS: We surveyed a nationally representative sample of diagnostic radiologists. Of 381 eligible radiologists, 312 (82%) responded. Descriptive statistics and chi-square tests were used to assess radiologists' opinions about double-contrast barium enema volume and capacity and to compare radiologists' beliefs about colorectal cancer screening with those of primary care physicians. Logistic regression was used to identify characteristics of radiologists who receive referrals for or perform a higher volume of screening double-contrast barium enema and of those who expect the volume of double-contrast barium enemas to increase. RESULTS: Seventy-five percent of radiologists said that double-contrast barium enema is a "very effective" colorectal cancer screening procedure compared with 33% of primary care physicians. Although 86% of radiologists reported performing one or more screening double-contrast barium enema procedures during a typical month, only 27% indicated that they did so 11 or more times. Fifteen percent of radiologists said that their double-contrast barium enema volume had increased over the past 3 years, and 50% expect an increase over the next 3 years. Only 8% said that the capacity of facilities and personnel to meet the demand for double-contrast barium enemas in their geographic area of practice is inadequate. Geographic region and belief in double-contrast barium enema efficacy were predictors of double-contrast barium enema volume and referrals. CONCLUSION: Most diagnostic radiologists perform colorectal cancer screening with double-contrast barium enema, but procedure volumes are modest. Because primary care physicians view double-contrast barium enema less positively than do radiologists, radiologists' expectations for an increased volume of double-contrast barium enemas over the next few years may not be realized.

Adult↗
PubMedDate not supplied

Automated external defibrillator deployment in high schools and senior centers.

BACKGROUND: Policymakers with limited funds have been forced to make difficult decisions regarding which sites merit automated external defibrillators (AEDs). Guidelines have recommended that the allocation of AEDs be based largely on the site-specific risk of sudden cardiac death (cardiac arrest), with devices preferentially located at high-risk venues. However, there are limited data on whether such a strategy is being followed. The authors surveyed low-risk (schools) and high-risk (senior centers) venues to assess the availability of AEDs. METHODS: A random sample of 200 high schools was identified; 12 were excluded, resulting in a final sample of 188. Each was contacted to determine the number of students, number of teachers, availability of AEDs, and number of cardiac arrests during the 2001-02 academic year. For comparison, 20 licensed senior centers were surveyed to assess the availability of AEDs. RESULTS: Among 147 schools that responded to the survey, the mean student enrollment was 1,117 and the mean number of teachers was 58. There were three reported cases of cardiac arrest (2 students, 1 teacher), resulting in an annual incidence of cardiac arrest in a school of 2.1% (95% confidence interval [CI] 0.4%-5.7%). Thirty-seven schools (25%; 95% CI 18%-33%) reported having AEDs and 35 (27%) intended to purchase them. In contrast, among 20 senior centers, AEDs were available at two (10%; 95% CI 1%-32%), and the and there were four reported cardiac arrests (annual incidence 20%). CONCLUSION: The availability of AEDs across different sites may not correspond directly to the risk of cardiac arrest at these sites.

Adolescent↗