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R Ryan

Publications and source records attributed to R Ryan.

At least 19 recordsLinked to original sources
PubMed2006

Gene therapy for prostate cancer: current strategies and new cell-based approaches.

Prostate cancer is the most commonly diagnosed cancer in adult males in the Western world. It accounts for one in ten cancer cases and is the second leading cause of cancer death in men, after lung cancer. A number of curative treatments are available for patients with localized prostate cancer such as radical prostatectomy, radiotherapy, or brachytherapy. However, a proportion of these men will develop progressive disease, and some will present de novo with advanced and metastatic prostate cancer, which is amenable to palliation only with androgen-withdrawal therapy. Most of these patients will eventually develop hormone refractory disease which is incurable, and for whom gene therapy, if feasible may develop as an alternative treatment option. In this review we discuss the gene therapy vectors and strategies that are currently in use, new cell-based approaches, discuss their advantages and disadvantages, and review the potential or proven pre-clinical and clinical efficacy in prostate cancer models/patients.

Adult↗
PubMed2005

New cases of diabetes mellitus in England and Wales, 1994-1998: database study.

OBJECTIVE: The objective of this study was to estimate the annual rate of diagnosis of new cases of diabetes mellitus in England and Wales, and the number of new cases in each year. STUDY DESIGN: Cohort study. METHOD: Analysis of electronic patient records from the General Practice Research Database, using 208 general practices with a total list size of 1.3 million patients. RESULTS: We estimate that the national rate of diagnosis of new cases of diabetes in England and Wales was 17.5 [95% confidence intervals (CI) 16.6--18.4] per 10,000 person-years in 1994 and 22.1 (95%CI 21.2--23.0) per 10,000 person-years in 1998. We estimate that there were 87,642 new cases of diabetes mellitus in England and Wales in 1994 and 111,345 in 1998. CONCLUSIONS: We estimate that the rate at which new cases of diabetes were diagnosed rose by about 26% in England and Wales from 1994 to 1998. This conclusion was unchanged when we took account of the ageing of the national populations between the beginning and end of the study period. We estimate that the number of new cases of diabetes diagnosed each year in England and Wales also increased by one-quarter over the same period. If the number of cases and the rate at which they are diagnosed continues to increase, this will need to be considered by those planning services for people with diabetes.

Adolescent↗
PubMed2005

Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

AIMS: To standardize the pathological analysis of total mesorectal excision specimens of rectal cancer following neoadjuvant chemoradiotherapy for locally advanced disease (T3/T4), including tumour regression. METHODS AND RESULTS: Standardized dissection and reporting was used for 60 patients who underwent total mesorectal excision following long-course chemoradiotherapy. Tumour regression was scored by two pathologists (K.S., D.G.) using both an established 5-point tumour regression grade (TRG), and a novel 3-point grade. Both scores were evaluated for interobserver variability. A complete or near-complete pathological response (3-point TRG 1) was found in 10 patients (17%). Using the 5-point TRG, there was good agreement between both pathologists (kappa = 0.64). Using the 3-point grade, agreement was excellent (kappa = 0.84). No disease recurrence has been reported in patients with a complete, or near complete pathological response (3-point TRG 1), after a mean follow-up of 22 months. CONCLUSION: Tumour regression grade is a useful method of scoring tumour response to chemoradiotherapy in rectal cancer. TRG 1 and 2 can be regarded as a complete pathological response (ypT0). A modified 3-point grade has the advantage of better reproducibility, with similar prognostic significance.

Adult↗
PubMed2004

EtCRK2, a cyclin-dependent kinase gene expressed during the sexual and asexual phases of the Eimeria tenella life cycle.

EtCRK2, a cyclin-dependent kinase from the coccidian parasite, Eimeria tenella is closely related to eukaryotic cyclin-dependent kinases that regulate progression of the cell cycle and to several cyclin-dependent kinases identified in the Apicomplexa. Northern blot analyses revealed that EtCRK2 is transcribed during both asexual (first-generation schizogony) and sexual (oocyst sporulation) replicative phases of the parasite life cycle. In addition, it appears to be transcriptionally regulated during meiosis. Recombinant EtCRK2 produced in Escherichia coli has kinase activity which is significantly stimulated by the addition of vertebrate cyclin A. This cyclin-dependent kinase may play a significant role in regulating critical cell cycle events during both asexual proliferation and sexual development of the parasite.

Amino Acid Sequence↗
PubMed2004

Eletriptan for the acute treatment of migraine: results of bridging a Japanese study to Western clinical trials.

OBJECTIVE: To compare the efficacy, safety and tolerability of eletriptan (20, 40 and 80 mg) to placebo when given to Japanese and Western patients for the acute treatment of migraine. METHODS: A double-blind, randomized, parallel-group trial with the aforementioned therapeutic objectives was conducted in Japan (N = 321). By bridging analysis, data from this study were compared to two migraine trials previously conducted in the US (N = 1190) and Europe (N = 563). RESULTS: The 2-h post-dose headache response rates (i.e., the primary efficacy endpoint) of Japanese migraineurs to eletriptan 20, 40 and 80 mg were 64, 67 and 76%, respectively; European and American migraineurs showed similar trends and, in these studies, eletriptan was significantly superior to placebo (p < 0.05). Japanese patients did demonstrate a higher placebo response than Westerners, possibly due to differences in previous triptan exposure or expectation. Adverse events were generally mild to moderate, were comparable in all three studies, and showed a modest dose-response effect. CONCLUSION: The efficacy and tolerability of eletriptan for the acute treatment of migraine is comparable in Japan, Europe and the US.

Adolescent↗
PubMed2004

Bowel evisceration.

Explore the source record for details and available documents.

Endometrial Neoplasms↗
PubMed2004

An evaluation of left sided colonic polyps as a marker for right sided cancers.

The detection of a left-sided polyp on flexible sigmoidoscopy has been suggested as providing a heralding sign for right-sided tumours. We assessed our own experience with right-sided colonic cancers with reference to detection modality, surgical intervention and their association with left-sided polyps. We performed a retrospective review of a prospectively collected colorectal cancer database, with endoscopic and radiological records. Patients were subcategorised on the basis of the presence or absence of left-side polyps. Ninety-one consecutive patients who underwent curative surgery for right-sided colonic cancers were studied. Endoscopy was used to detect right-sided carcinomas in 10 (83%) of the 12 cases with synchronous left-sided polyps and radiological imaging utilised in 2 cases. In patients without evidence of left sided disease endoscopy was used in 40 (51%) of the 79 patients. In our experience most right sided cancers do not have a synchronous polyp evident on the left side 79 (87%).

Adult↗
PubMed2002

Clinical efficacy of frovatriptan: placebo-controlled studies.

OBJECTIVE: To confirm the clinical efficacy of frovatriptan 2.5 mg. BACKGROUND: Frovatriptan is a new 5-hydroxytryptamine (5-HT)(1B/1D) receptor agonist being developed for the acute treatment of migraine with or without aura. Results from preclinical and clinical pharmacology studies showed frovatriptan to be a potent 5-HT(1B) receptor agonist with a long terminal elimination half-life (26 hours) and a broad therapeutic index. DESIGN: Three randomized, placebo-controlled, double-blind, parallel-group trials, in a total of 2676 patients, were performed to confirm the clinical efficacy of frovatriptan 2.5 mg for the acute treatment of migraine. RESULTS: In all three studies, headache response 2 hours after frovatriptan dosing was significantly greater than that seen with placebo (P < or = .001) with approximately a two-fold measure of effect over placebo for headache response at 2 and 4 hours postdosing. Time to headache response occurred within 1.5 hours in a substantial proportion of patients. The incidence of 24-hour headache recurrence with frovatriptan was low (10% to 25%). Frovatriptan therapy also was associated with a high degree of patient satisfaction. CONCLUSIONS: Frovatriptan represents a consistently effective acute treatment for migraine and accompanying symptoms.

Adult↗
PubMed2001

Taf(II) 250 phosphorylates human transcription factor IIA on serine residues important for TBP binding and transcription activity.

Transcription factor IIA (TFIIA) is a positive acting general factor that contacts the TATA-binding protein (TBP) and mediates an activator-induced conformational change in the transcription factor IID (TFIID) complex. Previously, we have found that phosphorylation of yeast TFIIA stimulates TFIIA.TBP.TATA complex formation and transcription activation in vivo. We now show that human TFIIA is phosphorylated in vivo on serine residues that are partially conserved between yeast and human TFIIA large subunits. Alanine substitution mutation of serine residues 316 and 321 in TFIIA alphabeta reduced TFIIA phosphorylation significantly in vivo. Additional alanine substitutions at serines 280 and 281 reduced phosphorylation to undetectable levels. Mutation of all four serine residues reduced the ability of TFIIA to stimulate transcription in transient transfection assays with various activators and promoters, indicating that TFIIA phosphorylation is required globally for optimal function. In vitro, holo-TFIID and TBP-associated factor 250 (TAF(II)250) phosphorylated TFIIA on the beta subunit. Mutation of the four serines required for in vivo phosphorylation eliminated TFIID and TAF(II)250 phosphorylation in vitro. The NH(2)-terminal kinase domain of TAF(II)250 was sufficient for TFIIA phosphorylation, and this activity was inhibited by full-length retinoblastoma protein but not by a retinoblastoma protein mutant defective for TAF(II)250 interaction or tumor suppressor activity. TFIIA phosphorylation had little effect on the TFIIA.TBP.TATA complex in electrophoretic mobility shift assay. However, phosphorylation of TFIIA containing a gamma subunit Y65A mutation strongly stimulated TFIIA.TBP.TATA complex formation. TFIIA-gammaY65A is defective for binding to the beta-sheet domain of TBP identified in the crystal structure. These results suggest that TFIIA phosphorylation is important for strengthening the TFIIA.TBP contact or creating a second contact between TFIIA and TBP that was not visible in the crystal structure.

Amino Acid Sequence↗
PubMed2001

Genomic organisation and developmentally regulated expression of an apicomplexan aspartyl proteinase.

The cDNA for an aspartyl proteinase, termed eimepsin, was isolated from an Eimeria tenella sporulated oocyst library and the deduced amino acid sequence found to be almost identical to a previously described aspartyl proteinase from E. acervulina (97.4% amino acid identity). An E. tenella cosmid clone covering the entire eimepsin gene was cloned and characterised. Sequencing revealed that the eimepsin gene spans 2.9 kb and consists of 18 exons and 17 introns. The 5' flanking region sequence of the gene contains a putative transcriptional promoter sequence (TATAAA box) and three potential transcription initiator sites (Inr sites). Expression of eimepsin at the mRNA and protein level is developmentally regulated during oocyst sporulation. The eimepsin transcript was detected in unsporulated oocysts and increased in abundance during the early part of sporulation when the oocyst undergoes nuclear division and blast formation. Thereafter, the level of the eimepsin transcript decreases and in the excysted sporozoite, no eimepsin-specific RNA was detected. Expression of eimepsin lags behind transcript expression by some hours, and the protein accumulates in the oocyst during sporocyst and sporozoite formation.

Amino Acid Sequence↗
PubMed2001

Physician unwitting participation in abuse and neglect of persons with developmental disabilities.

The vast majority of birth parents and foster parents for children with special needs do the best they can in challenging circumstances. Many describe the frustrating circumstance of knowing more than their physicians about their child's unusual medical conditions. In general, physicians are well-advised to listen carefully to the reports of observant, caring parents and foster parents, and to give these observations at least as much weight as their own. However, in the work of our traveling clinic we have observed a number of situations of abuse and neglect which were perpetrated by parents or foster parents, and where the actual acts of abuse and/or neglect were wholly or in part endorsed, in writing, by the treating physician.

Adolescent↗
PubMed2001

Diagnosis of babesiosis using an immunoblot serologic test.

Although the current indirect immunofluorescent assay (IFA) diagnostic antibody test for human babesiosis is sensitive and specific, an immunoblot antibody test may be easier to standardize and to perform. Our objective, therefore, was to determine the efficacy of and develop interpretive criteria for an immunoblot antibody test for diagnosing acute human babesiosis using a Babesia microti whole-cell lysate as the antigen. We compared the reactivity of sera to a B. microti immunoblot assay in 24 human subjects experiencing symptoms and expressing laboratory evidence of babesiosis, 28 subjects who experienced Lyme disease, 12 subjects who experienced human granulocytic ehrlichiosis, and 51 subjects who reported no history of any of these diseases and whose sera did not react against B. microti antigen in an IFA test. Immunoblot strips were impregnated with proteins derived from the GI strain of B. microti that had been electrophoresed in an acrylamide sodium dodecyl sulfate gel, followed by electroblotting onto nitrocellulose membranes. The sera of all subjects who experienced babesiosis reacted against the B. microti antigen in the IFA and against at least one of nine immunoblot protein bands specific to B. microti. In contrast, none of the sera from people who appeared not to have experienced this infection reacted against the B. microti antigen in the IFA (compared to 4% in the immunoblot assay). When two reactive bands were considered as definitive, immunoblot test sensitivity was 96%, while specificity was 99% and predictive positivity and predictive negativity were 96 and 99%, respectively. Our B. microti immunoblot procedure shows promise as a sensitive, specific, and reproducible assay for routine clinical diagnosis of acute babesiosis.

Antibodies, Protozoan↗
PubMed2001

Management of paediatric otitis media with effusion in the UK: a survey conducted with the guidance of the Clinical Effectiveness Unit at the Royal College of Surgeons of England.

A survey was undertaken of the practice of all Otorhinolaryngologists in England and Wales looking both at practice in general and at management of individual patients, including a patient satisfaction questionnaire, under the auspices of the Clinical Effectiveness Unit at the Royal College of Surgeons. Postal questionnaires enquired about practice in general and management in particular of 20 sequential patients per consultant. Parent questionnaires were sent six weeks and one year post-operatively. Ninety consultants took part and 1503 individual patient proformas were returned. Results showed that these consultants are managing children with otitis media with effusion (OME) in a manner very close to the recommendations of the Effective Healthcare Bulletin (1992) and consistent with the recent Clinical Effectiveness Statement of the BAOHNS, and that the intervention is popular with parents.

Child↗
PubMed2000

Mapping and expression of microneme genes in Eimeria tenella.

Microneme organelles are located at the apical tip of invading stages of all apicomplexan parasites and they contain proteins that are critical for parasite adhesion to host cells. In this paper, we have utilised the process of oocyst sporulation in Eimeria tenella to investigate the timing of expression of components of the microneme organelle, at both mRNA and protein levels. Two time-course studies showed that there is a high level of synchrony in the sporulation process, especially during the time period when sporozoites are formed. Western blotting showed that the expression of five microneme proteins (EtMIC1-5) is differentially regulated and highly co-ordinated during sporulation with the proteins being detected only towards the end of the process, as the sporozoites matured within the sporocysts. In contrast, mRNA for all five of these microneme proteins was detected some 10-12 h earlier in sporulation than when the corresponding proteins were seen. Overall these data suggest that the expression of proteins destined for the microneme is regulated both at the transcriptional and translational level. The single copy genes encoding EtMIC1-5 are not clustered on the genome, but are found on four different chromosomes.

Animals↗
PubMed2000

Association between delirium and death in AIDS patients.

The purpose of this study was to examine the relationship between delirium and death in AIDS patients. Forty-one patients admitted to a combination skilled nursing and assisted-living facility in 1994 were included in the retrospective chart review. Patients were grouped according to the presence versus absence of delirium during the first week of admission. Demographic characteristics and medical morbidity of the two groups were compared using the Chi-square statistic. Kaplan-Meier survival analysis was used to estimate survival functions during the study period for the delirious and nondelirious groups. Nine patients (22%) were found to have an episode of delirium in the first week of admission. There were no significant differences in demographic characteristics or medical morbidity between the delirious and nondelirious groups. Median days from admission to death for those with delirium (10 days) versus those without delirium (135 days) was significantly different (log rank = 19.03; p < 0.0001). Authors concluded that delirium is a marker for decreased survival in this sample of AIDS patients. Future research needs to demonstrate whether improved care of AIDS patients can prevent delirium or limit adverse outcomes associated with it.

Acquired Immunodeficiency Syndrome↗