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J M O'Sullivan

Publications and source records attributed to J M O'Sullivan.

13 recordsLinked to original sources
PubMed2006

A phase 2 study of high-activity 186Re-HEDP with autologous peripheral blood stem cell transplant in progressive hormone-refractory prostate cancer metastatic to bone.

PURPOSE: We investigated the potential for improvement in disease control by use of autologous peripheral blood stem cell transplant (PBSCT) to permit administration of high activities of (186)Re-hydroxyethylidene diphosphonate (HEDP) in patients with progressive hormone-refractory prostate cancer (HRPC). METHODS: Eligible patients had progressive HRPC metastatic to bone, good performance status and minimal soft tissue disease. Patients received 5,000 MBq of (186)Re-HEDP i.v., followed 14 days later by PBSCT. Response was assessed using PSA, survival, pain scores and quality of life. RESULTS: Thirty-eight patients with a median age of 67 years (range 50-77) and a median PSA of 57 ng/ml (range 4-3,628) received a median activity of 4,978 MBq (186)Re-HEDP (range 4,770-5,100 MBq). The most serious toxicity was short-lived grade 3 thrombocytopenia in 8 (21%) patients. The median survival of the group is 21 months (95%CI 18-24 months) with Kaplan-Meier estimated 1- and 2-year survival rates of 83% and 40% respectively. Thirty-one patients (81%, 95% CI 66-90%) had stable or reduced PSA levels 3 months post therapy while 11 (29%, 95% CI 15-49%) had PSA reductions of >50% lasting >4 weeks. Quality of life measures were stable or improved in 27 (66%) at 3 months. CONCLUSION: We have shown that it is feasible and safe to deliver high-activity radioisotope therapy with PBSCT to men with metastatic HRPC. Response rates and survival data are encouraging; however, further research is needed to define optimal role of this treatment approach.

Aged↗
PubMed2003

Broadening the criteria for avoiding staging bone scans in prostate cancer: a retrospective study of patients at the Royal Marsden Hospital.

OBJECTIVE: To determine if it is possible to exclude staging bone scans in a greater proportion of patients if more consideration is given to T stage and Gleason score, as recent guidelines from the National Institute of Clinical Excellence state that routine staging bone scans for prostate cancer are unnecessary in patients with a prostate specific antigen level (PSA) of < 10 ng/mL and Gleason scores of < 8. PATIENTS AND METHODS: We identified a cohort of consecutive patients with untreated prostate cancer who had a staging isotope bone scan between 1 January 1995 and 31 December 2000, who were not on hormone therapy, who had their PSA estimated within 30 days of the scan, and who had histologically confirmed prostate cancer on biopsy reviewed at the Royal Marsden. Data were analysed according to Gleason score, major Gleason grade, clinical T-stage and PSA level. RESULTS: In all, 420 patients were identified who fulfilled the criteria for inclusion; 67 scans (16%, 95% confidence interval, CI, 13-20%) were positive. Of the 187 scans taken in patients with a PSA level of <or= 20 ng/mL, stage < T4 and Gleason < 8 (with major Gleason grade < 4), two (1%, 0.3-4%) were reported as positive, giving a negative predictive value of 99% (95% CI 98.5-99.5%) for these criteria for avoiding the need for staging bone scans. In 116 patients (28%) with Gleason score 7, of whom 28 (24%) had positive scans, there was a statistically significant association between positive scans and a major Gleason pattern of 4 compared with 3. CONCLUSIONS: Isotope bone scans are an unnecessary part of staging of prostate cancer if the PSA level is <or= 20 ng/mL, stage < T4 and Gleason score < 8, and should be omitted unless the major Gleason pattern is 4. The present results suggest that by considering the Gleason score and T stage, a larger proportion of patients with prostate cancer than previously thought could avoid a staging bone scan.

Aged↗
PubMed2003

Predicting the risk of bleomycin lung toxicity in patients with germ-cell tumours.

BACKGROUND: Bleomycin pulmonary toxicity (BPT) has been known since the early clinical trials of bleomycin in the 1960s. Postulated risk factors include cumulative bleomycin dose, reduced glomerular filtration rate (GFR), raised creatinine, older age and supplemental oxygen exposure. PATIENTS AND METHODS: From our prospectively collected testicular cancer research database, we reviewed 835 patients treated at the Royal Marsden NHS Trust (Sutton, UK) with bleomycin-containing regimens for germ-cell tumours between January 1982 and December 1999, to identify those with BPT. RESULTS: Fifty-seven (6.8%) patients had BPT, ranging from X-ray/CT (computed tomography) changes to dyspnoea. There were eight deaths (1% of patients treated) directly attributed to BPT. The median time from the start of bleomycin administration to documented lung toxicity was 4.2 months (range 1.2-8.2). On multivariate analysis, the factors independently predicting for increased risk of BPT were GFR <80 ml/min [hazard ratio (HR) 3.3], age >40 years (HR 2.3), stage IV disease at presentation (HR 2.6) and cumulative dose of bleomycin >300,000 IU (HR 3.5). CONCLUSIONS: Patients with poor renal function are at high risk of BPT, especially if they are aged >40 years, have stage IV disease at presentation or receive >300,000 IU of bleomycin. In such cases alternative drug regimens or dose restriction should be considered.

Adolescent↗
PubMed2002

High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone.

We tested the feasibility and toxicity of high activities Rhenium-186 hydroxyethylidene diphosphonate, with peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. Twenty-five patients received between 2500 and 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate followed 14 days later by the return of peripheral blood peripheral blood stem cells. Activity limiting toxicity was defined as grade III haematological toxicity, lasting at least 7 days, or grade IV haematological toxicity of any duration or any serious unexpected toxicity. Activity limiting toxicity occurred in two of six who received activities of 5000 MBq and maximum tolerated activity was defined at this activity level. Prostate specific antigen reductions of 50% or more lasting at least 4 weeks were seen in five of the 25 patients (20%) all of whom received more than 3500 MBq of Rhenium-186 hydroxyethylidene diphosphonate. The actuarial survival at 1 year is 54%. Administered activities of 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate are feasible using autologous peripheral blood peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. The main toxicity is thrombocytopaenia, which is short lasting. A statistically significant activity/prostate specific antigen response was seen. We have now commenced a Phase II trial to further evaluate response rates.

Bone Neoplasms↗
PubMed2002

A review of the efficacy of bone scanning in prostate and breast cancer.

Bone scintigraphy has provided valuable data in the assessment and management of neoplastic disease since being first described in the early 1960s. There have been many developments in imaging techniques and radiopharmaceuticals over the years allowing more reliable detection of metastatic spread to bone. Other imaging modalities are also evolving roles in the detection of metastatic spread including computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Despite this, isotope bone scans continue to have a central role in detection and surveillance of bone metastases in breast and prostate cancer. Paralleling developments in imaging there have been enormous changes in the treatment options available for cancers of the breast and prostate that have metastasised to bone. Bone specific treatments including radionuclides and bisphosphonates as well as high dose chemotherapy provide potential improvement in disease control. There is also evidence that earlier treatment of bone metastases may prolong survival. This increases the need for efficient methods of detection and monitoring of disease. In this article we discuss the efficacy of bone scintigraphy in breast and prostate cancer from the point of view of staging, systematic follow-up of asymptomatic patients, evaluation of symptomatic patients and the assessment of response to therapy.

Bone Neoplasms↗
PubMed2001

The Candida albicans gene encoding the cytoplasmic leucyl-tRNA synthetase: implications for the evolution of CUG codon reassignment.

In a number of Candida species the 'universal' leucine codon CUG is decoded as serine. To help understand the evolution of such a codon reassignment we have analyzed the Candida albicans leucyl-tRNA synthetase (CaLeuRS) gene (CaCDC60). The predicted CaLeuRS sequence shows a significant level of amino acid identity to LeuRS from other organisms. A mitochondrial LeuRS (ScNAM2) homologue, which shared low identity with the CaLeuRS, was also identified in C. albicans. Antigenically-related LeuRSs were identified in a range of Candida species decoding the CUG codon as both serine and leucine, using an antibody raised against the N-terminal 15 amino acids of the CaLeuRS. Complementation experiments demonstrated that the CaLeuRS was able to functionally complement a Saccharomyces cerevisiae cdc60::kanMX null mutation. We conclude that there is no alteration in tRNA recognition and aminoacylation by the C. albicans LeuRS, which argues against it having a role in codon reassignment. The nucleotide sequences of the CaCDC60 and CaNAM2 genes were deposited at GenBank under Accession numbers AF293346 and AF352020, respectively.

Amino Acid Sequence↗
PubMed2001

Seryl-tRNA synthetase is not responsible for the evolution of CUG codon reassignment in Candida albicans.

A number of Candida species translate the standard leucine-CUG codon as serine using a novel ser-tRNA(CAG). This tRNA, which has an unusual anticodon stem-loop structure, has been implicated in the evolution of this codon reassignment. However, such a sense codon reassignment might also require a change in the specificity of the cognate aminoacyl tRNA-synthetase, in this case the ser-tRNA synthetase. Here we describe the cloning and sequence analysis of the C. albicans seryl aminoacyl-tRNA synthetase (CaSerRS) gene (CaSES1). The predicted CaSerRS sequence shows a significant level of amino acid identity to SerRs from other organisms and fully complements a S. cerevisiae SerRS null strain without any apparent defect in growth rate. This suggests that the SerRS recognizes and charges S. cerevisiae ser-tRNAs with similar efficiency to that of the S. cerevisiae SerRS. Using an antibody raised against CaSerRS, we also demonstrate the presence of SerRS in a range of Candida spp. showing CUG codon reassignment. We conclude that the key element in CUG reassigment in Candida spp. is the tRNA that decodes the CUG codon rather than a SerRS structural change. The nucleotide sequence of the CaSES1 gene has been deposited at GenBank under Accession No. AF290915.

Amino Acid Sequence↗
PubMed2001

Codon reassignment and the evolving genetic code: problems and pitfalls in post-genome analysis.

The in silico translation of open reading frames, using the 'universal genetic code', must be approached with caution. The uncovering of a number of codon reassignments in nuclear and organellar genomes highlights the importance of experimentally confirming the assignments of all 64 codons for the species whose genome is under investigation. Such alterations to codon meaning also suggest that the genetic code is not 'frozen' and continues to evolve.

Codon↗
PubMed2000

Complications of treatment with local field external beam radiotherapy for localized prostate cancer.

We performed this analysis to document the rate and severity of complications both during and after local field irradiation for localized prostate cancer and to assess the influence of three-dimensional conformal radiation therapy (3DCRT) on these complications. Bowel, urinary and cutaneous toxicities were noted in all patients treated with primary radiotherapy (RT) for prostate cancer using Radiation Therapy Oncology Group/European Organization for Research on Treatment of Cancer scores. Evaluations were performed weekly during RT, 6 weeks after RT and 3 monthly thereafter. Data on 111 were analysed. We also compared the complications of conventional and 3DCRT. The serious complication rates identified in this study compare favourably with those reported in the literature. Only 3.6%, 0.8% and 0% had acute grade 3 or 4 urinary, bowel or skin reactions respectively. Only two patients had chronic grade 3 or 4 urinary complications. Thus far no patients have developed chronic bowel or skin complications greater than grade 2. Despite dose escalation from 66 Gy to 70 Gy (with 3DCRT), there was a trend towards reduced toxicity when 3DCRT was compared with conventional radiation. RT is a well-tolerated treatment for early stage carcinoma of the prostate and our complication rates are compatible with international experiences. Further follow-up is required to determine the efficacy of treatment, the incidence of impotence and the final number of late complications.

Adenocarcinoma↗
PubMed2000

Candida albicans: adherence, signaling and virulence.

The focus of this symposium was to present new information on the morphogenesis of Candida albicans, particularly how it relates to signal transduction pathways and other genes involved in the regulation of morphogenesis. In addition, we discuss the role of adherence and colonization of the oral cavity by the organism and discuss the role of mannan as an adhesin that recognizes the human red blood cell. C. albicans utilizes at least two signal pathways to regulate its conversion from a yeast form to filamentous growth (hyphae). One of these two pathways is similar to the Saccharomyces cerevisiae pseudohyphal/mating pathway, which utilizes the regulatory protein, Cphlp. The other pathway is not totally defined but requires a second regulatory protein, referred to as Efg1p. Other signal pathways may exist, which include a two-component histidine kinase and response regulator proteins. The latter pathway(s) may include proteins such as Chk1p, Ssk1p, Shi1p and Cos1p/Nik1p. Mutations in strains, which specifically target these proteins, result in morphogenesis defects and avirulence or attenuation of strains. A growth regulatory gene has also been recently defined whose expression is associated with growth cessation and which appears to be a necessary prerequisite in conversion of the organism to a filamentous growth form. Starvation of yeast cells induces exponentially grown cells (and usually non-germinative) to germinate. This phenomenon is also observed in cells that are transiently treated with metabolic inhibitors. During each of these treatments (starvation, metabolic inhibition), expression of a growth regulatory gene (CGRI) increases. Adherence of C. albicans to host cells and tissues is complex; several proteins, which appear to have host recognition functions, have been defined. In the oral cavity, C. albicans selectively adheres to salivary proteins, which are absorbed to many oral surfaces. This mechanism enables the cells to colonize surfaces of the oral cavity. An understanding of these interactions may lead to strategies to prevent oral disease. Mannan from C. albicans may provide a host recognition function for C. albicans. Recent experiments indicate that mannan binds to human red blood cells and causes hemolysis. Binding of mannan to the band 3 protein of human red blood cells has been established. This activity may be associated with the ability of the organism to utilize hemoglobin (and iron).

Candida albicans↗
PubMedDate not supplied

Patterns of patient presentation to a Dublin urban emergency department with assault related injuries.

After perceiving an increase in the number of patients attending a large urban Irish Emergency Department (ED) with injuries sustained in assaults, the authors sought to examine the issue. A prospective observational study was conducted to look at the demographic profiles of victim and perpetrator, at rates of crime reporting and at the level of follow-up care arranged in the ED. Those most commonly assaulted were young Irish males who usually sustained head or facial injuries during weekend nights. Glass was the weapon most often used. Less than two-thirds of all victims planned to report the incident to the Garda Siochana (the Irish national police force). Women assaulted by their partners were least likely to involve the police. One fifth of patients required admission. Violence in Dublin's inner city is now a major health issue.

Adolescent↗