Biomedical subjects

Peter O'Donovan

Publications and source records attributed to Peter O'Donovan.

4 recordsLinked to original sources

PubMed2006

Novel DNA lesions generated by the interaction between therapeutic thiopurines and UVA light.

The therapeutic effect of the thiopurines, 6-thioguanine (6-TG), 6-mercaptopurine, and its prodrug azathioprine, depends on the incorporation of 6-TG into cellular DNA. Unlike normal DNA bases, 6-TG absorbs UVA radiation, and UVA-mediated photochemical damage of DNA 6-TG has potentially harmful side effects. When free 6-TG is UVA irradiated in solution in the presence of molecular oxygen, reactive oxygen species are generated and 6-TG is oxidized to guanine-6-sulfonate (G(SO3)) and guanine-6-thioguanine in reactions involving singlet oxygen. This conversion is prevented by antioxidants, including the dietary vitamin ascorbate. DNA G(SO3) is also the major photoproduct of 6-TG in DNA and it can be selectively introduced into DNA or oligonucleotides in vitro by mild chemical oxidation. Thermal stability measurements indicate that G(SO3) does not form stable base pairs with any of the normal DNA bases in duplex oligonucleotides and is a powerful block for elongation by Klenow DNA polymerase in primer extension experiments. In cultured human cells, DNA damage produced by 6-TG and UVA treatment is associated with replication inhibition and provokes a p53-dependent DNA damage response.

Antimetabolites, Antineoplastic↗

PubMed2006

Ambulatory hysteroscopy: evidence-based guide to diagnosis and therapy.

Healthcare providers are facing increasing demands for improvement in quality of life for patients. Improvements in service provision for women are being ensured by the introduction of minimally invasive technologies into all spheres of gynaecologic practice. Ambulatory hysteroscopy (direct endoscopic visualization of the endometrial cavity) is an extremely exciting and rapidly advancing field of gynaecologic practice. It advanced dramatically during the 1990s, shifting the focus in healthcare away from inpatient diagnosis and treatment. Hysteroscopy is used extensively in the evaluation of common gynaecological problems that were previously evaluated with blind and inaccurate techniques (e.g. premenopausal menstrual disorders, infertility and postmenopausal bleeding). It allows direct visualization of the uterine cavity and the opportunity for targeted biopsy, safe removal of endometrial polyps, and treatment of submucous fibroids, septa and adhesions. Ambulatory hysteroscopy is safe, with a low incidence of serious complications; it has a small failure rate. There is a general consensus that hysteroscopy is the current gold standard for evaluating intrauterine pathology, including submucous myomas, polyps, hyperplasia and cancer. Hysteroscopy in the ambulatory setting appears to have an accuracy and patient acceptability equivalent to inpatient hysteroscopy under general anaesthetic. The primary goal of this chapter is to provide a high-quality, evidence-based text on ambulatory diagnostic and operative hysteroscopy. The chapter includes in-depth analysis of the indications for outpatient hysteroscopy, its contraindications, the accuracy of diagnostic hysteroscopy, relevant risk management issues and, training and teaching.

Ambulatory Care↗

PubMed2005

Azathioprine and UVA light generate mutagenic oxidative DNA damage.

Oxidative stress and mutagenic DNA lesions formed by reactive oxygen species (ROS) are linked to human malignancy. Clinical treatments inducing chronic oxidative stress may therefore carry a risk of therapy-related cancer. We suggest that immunosuppression by azathioprine (Aza) may be one such treatment. Aza causes the accumulation of 6-thioguanine (6-TG) in patients' DNA. Here we demonstrate that biologically relevant doses of ultraviolet A (UVA) generate ROS in cultured cells with 6-TG-substituted DNA and that 6-TG and UVA are synergistically mutagenic. A replication-blocking DNA 6-TG photoproduct, guanine sulfonate, was bypassed by error-prone, Y-family DNA polymerases in vitro. A preliminary analysis revealed that in five of five cases, Aza treatment was associated with a selective UVA photosensitivity. These findings may partly explain the prevalence of skin cancer in long-term survivors of organ transplantation.

Adenine Phosphoribosyltransferase↗

PubMed2003

Endometrial ablation.

PURPOSE OF REVIEW: Although endometrial ablation has now been accepted practice for more than 20 years, it continues to be a source of research, controversy and speculation. This is illustrated by the 175 articles found in PubMed between the years 2000 and 2003 under the search term 'endometrial ablation' commissioned as part of the preparation for this article. RECENT FINDINGS: The so-called first-generation methods (laser, resection, rollerball) have now got long-term follow-up data of up to 20 years. A few of the second-generation devices have published long-term follow-up data of 5 years. All of the second-generation devices assessed in randomized trials with the first-generation methods compare favourably; however, there are few data on cost effectiveness. Similarly, there are few data comparing endometrial ablation with the Mirena intrauterine device. SUMMARY: Conventional endometrial ablation has been extensively validated; however, many of the newer techniques have inadequate patient numbers or lengths of follow-up on which to evaluate their long-term efficacy, safety or cost effectiveness fully. The anticipated decline in hysterectomy rates with the advent of endometrial destruction methods has not occurred, and this may indicate a lower threshold for surgical management.

Endometrium↗