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Biomedical subjects

J Ryan

Publications and source records attributed to J Ryan.

At least 19 recordsLinked to original sources

The influence of cyclosporin alone, or cyclosporin and methotrexate, on the incidence of mixed haematopoietic chimaerism following allogeneic sibling bone marrow transplantation for severe aplastic anaemia.

We previously reported a randomized trial comparing Cyclosporin-A (CsA) and short-term methotrexate versus CsA alone for graft-versus-host disease (GvHD) prophylaxis in 71 patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) from a human leucocyte antigen-identical sibling for severe aplastic anaemia (SAA). We found a better survival in the group receiving the two-drug prophylaxis regimen with no significant difference in the probability of developing GvHD between the two groups. The present study details chimaeric analysis and its influence on survival and GvHD occurrence in 45 of the original 71 patients in whom serial samples were available. Analysis was carried out in a blinded prospective manner. Seventy-two per cent achieved complete donor chimaerism (DC), 11% stable mixed chimaerism (SMC) and 17% progressive mixed chimaerism (PMC). The overall 5-year survival probability was 82% (+/-11%) with a significant survival advantage (P = 0.0009) in DC or SMC compared to those with PMC. Chronic GvHD was more frequent in DC patients, whereas no patient with SMC developed chronic GvHD. Graft failure occurred in 50% of the PMC group. This study demonstrates the relevance of chimaerism analysis in patients receiving HSCT for SAA and confirms the occurrence of mixed chimaerism in a significant proportion of recipients.

Adolescent↗

Clothing damage analysis in alleged sexual assaults--the need for a systematic approach.

Clothing damage analysis is an integral part of the examinations carried out in sexual assault type cases. This analysis can be used to corroborate different versions of events and is at its most powerful in elucidating false allegation cases and consent cases. The purpose of this study was to determine to what extent people with varying levels of forensic awareness, experience and training could correctly carry out damage analysis. Two participant groups were asked to take part in this study. Group A ('forensic group') comprised participants at a forensic science conference, and Group B ('student group') comprised students undertaking a degree course in Forensic Science. Each group was given a practical workshop consisting of a lecture outlining common fabric types and general features observed in different damage types. Each participant was subsequently shown 25 pieces of 'damage' and asked to identify both the type of fabric construction (knit or weave) and the type of damage (cut, tear, rip, wear and tear). The ability to identify fabric construction and damage types varied within the two groups studied and across the groups. The forensic group performed better both in fabric and damage assessment than the student group. This paper suggests a systematic approach to clothing damage analysis to maximise the benefits that can be obtained from this area of forensic science and to minimise the subjectivity within the field.

Adolescent↗

A relative reduction in mid-follicular LH concentrations during GnRH agonist IVF/ICSI cycles leads to lower live birth rates.

BACKGROUND: The effect of early- and mid-follicular LH concentrations on the ovarian response and pregnancy outcomes was evaluated in women receiving pituitary down-regulation with a GnRH agonist and ovarian stimulation with recombinant FSH (rFSH) during IVF/ICSI treatment. METHODS: Blood samples were collected prospectively from 701 cycles (560 patients) of assisted reproduction and analysed retrospectively. On the basis of LH concentrations on stimulation day 7/8, the patients were divided into two groups: LH<1.2 IU/l (n=179) and LH>or=1.2 IU/l (n=522). Cycle outcomes were also compared on the basis of a ratio of mid- to early-follicular LH concentrations ( 0.5, n=491). RESULTS: Patients with low LH concentrations were found to have a significant reduction in the late-follicular estradiol concentrations (P<0.001), the number of oocytes retrieved (P<0.01) and the number of usable embryos (P<0.01), and they required significantly more rFSH (430 IU difference, P<0.01). These differences did not translate into a significant change in live birth rates. Conversely, a ratio of or=50%) was associated with a significant reduction in live birth rates per embryo transfer and per cycle started (27.3 versus 19.0%, P<0.05 and 22.2 versus 15.8%, P<0.05, respectively). CONCLUSIONS: Low mid-follicular levels of LH have a significant impact on ovarian response but not on live birth rates. A fall in LH level of >or=50% from the early- to mid-follicular phase resulted in a lower live birth rate.

Adult↗

Wilms' tumor gene 1 (WT1) expression in childhood acute lymphoblastic leukemia: a wide range of WT1 expression levels, its impact on prognosis and minimal residual disease monitoring.

Wilms' tumor gene 1 (WT1) is overexpressed in the majority (70-90%) of acute leukemias and has been identified as an independent adverse prognostic factor, a convenient minimal residual disease (MRD) marker and potential therapeutic target in acute leukemia. We examined WT1 expression patterns in childhood acute lymphoblastic leukemia (ALL), where its clinical implication remains unclear. Using a real-time quantitative PCR designed according to Europe Against Cancer Program recommendations, we evaluated WT1 expression in 125 consecutively enrolled patients with childhood ALL (106 BCP-ALL, 19 T-ALL) and compared it with physiologic WT1 expression in normal and regenerating bone marrow (BM). In childhood B-cell precursor (BCP)-ALL, we detected a wide range of WT1 levels (5 logs) with a median WT1 expression close to that of normal BM. WT1 expression in childhood T-ALL was significantly higher than in BCP-ALL (P<0.001). Patients with MLL-AF4 translocation showed high WT1 overexpression (P<0.01) compared to patients with other or no chromosomal aberrations. Older children (> or =10 years) expressed higher WT1 levels than children under 10 years of age (P<0.001), while there was no difference in WT1 expression in patients with peripheral blood leukocyte count (WBC) > or =50 x 10(9)/l and lower. Analysis of relapsed cases (14/125) indicated that an abnormal increase or decrease in WT1 expression was associated with a significantly increased risk of relapse (P=0.0006), and this prognostic impact of WT1 was independent of other main risk factors (P=0.0012). In summary, our study suggests that WT1 expression in childhood ALL is very variable and much lower than in AML or adult ALL. WT1, thus, will not be a useful marker for MRD detection in childhood ALL, however, it does represent a potential independent risk factor in childhood ALL. Interestingly, a proportion of childhood ALL patients express WT1 at levels below the normal physiological BM WT1 expression, and this reduced WT1 expression appears to be associated with a higher risk of relapse.

Adolescent↗

Is antibiotic prophylaxis required for flexible cystoscopy? A truncated randomized double-blind controlled trial.

PURPOSE: To examine the incidence of urinary tract infection (UTI) after flexible cystoscopy (FC) and determine whether prophylactic norfloxacin reduces this incidence compared with placebo. PATIENTS AND METHODS: A double-blind trial was performed, randomizing 234 patients to either 400 mg of norfloxacin or placebo prior to FC. All patients provided a midstream urine specimen (MSU) before the procedure, as well as at day 3 and day 7 after FC. In addition, a telephone questionnaire was performed to correlate the nature and severity of any symptoms associated with UTI. RESULTS: Interim analysis was performed because of the low recruitment rate, and a significantly lower infection rate than expected meant that the trial was discontinued. There was one symptomatic UTI in the placebo group (0.82%) and one in the norfloxacin group (0.89%). The UTI in the placebo group was de novo, while the infection in the norfloxacin group was secondary to pre-FC bacteriuria. There was no difference in the infection rates in the two groups. The overall infection rate (de novo and secondary to existing bacteruria) after FC was 0.85%. CONCLUSION: Infection after flexible cystoscopy is rare and not associated with significant morbidity. A much larger study would be required to determine whether antibiotic prophylaxis significantly reduces the rate of postprocedure UTI.

Anti-Infective Agents↗

Parasuicide assessment in the emergency department.

Parasuicide is an important predictor of future suicide. We collected information on all parasuicides presenting to the emergency department of a general hospital over a 3-month period. We examined detection rates, referral patterns and compared emergency department risk assessments of parasuicide with those of the psychiatric liaison team. We detected 123 parasuicides. One hundred and five (85.4%) were detected in the emergency department. Ninety-five (77.2%) were referred to the liaison psychiatry service. Liaison psychiatric risk assessment agreed with emergency department risk assessment in all cases that emergency doctors judged to be at low risk of suicide. However in cases that emergency doctors judged to be high risk the liaison assessment agreed in only 38.5% of cases. Emergency doctors appear to be appropriately cautious in their assessment of risk. However, parasuicides regularly go undetected in hospital and are not always referred for psychiatric evaluation when detected. More training in the detection, assessment and management of parasuicide is required for emergency doctors.

Adolescent↗

Evaluation of brucellosis RB51 vaccine for domestic water buffalo (Bubalus bubalis) in Trinidad.

Thirty-two young domestic water buffalo (Bubalus bubalis) were obtained from a brucellosis-free farm to determine effectiveness of RB51 vaccination for prevention of Brucella infection under natural-exposure conditions in Trinidad. Study animals (20 males and 12 females 5-20 months old) were assigned to vaccination or control groups, using a block randomization design ensuring equal sex distributions between groups. The vaccination group received commercially available RB51 at the recommended calfhood dose of (1.0-3.4)x10(10) colony-forming units (CFU) and controls received 2ml sterile saline. Vaccination did not result in positive serologic results as measured by four traditional agglutination tests: standard tube agglutination test (STAT), standard plate agglutination test (SPAT), buffered plate agglutination test (BPAT), and card agglutination. Study animals were maintained in a brucellosis-positive herd in southern Trinidad with an estimated 56% prevalence to allow for natural exposure to B. abortus, which was evaluated using STAT, SPAT, BPAT, and card tests. Animals were sampled seven times over 2 years and were classified as positive if they had persistent agglutination titers or had Brucella isolated from specimens collected at completion of the study. Five of the original 32 study animals were lost to follow-up during the field trial. Six of the 14 (43%) vaccinated animals completing the study were classified as positive for Brucella infection-as were two of the 13 (15%) control animals (P=0.21). Isolates from four vaccinates and one control were confirmed as B. abortus biovar 1.

Animals↗

The frequency of the canine leukocyte adhesion deficiency (CLAD) allele within the Irish Setter population of Australia.

OBJECTIVE: To determine the frequency of the 107G-->C canine leukocyte adhesion deficiency (CLAD) mutation in Irish Setters from the Australian breeding population. METHOD: Genomic DNA was isolated from 87 Irish Setter blood samples and a region of the beta-2 integrin gene (ITGB2), encompassing the mutation, was amplified using real-time Polymerase Chain Reaction (PCR). Two fluorescently labelled probes were hybridised to the fragment, and fluorescence resonance energy transfer (FRET) was used to detect the 107G-->C mutation responsible for CLAD. RESULTS: Three new heterozygotes were identified among 87 healthy Irish Setters from Australia. All originated from a litter sired by a known heterozygote. A total of seven heterozygotes have now been identified in 92 dogs (7.6%), representing over 90% of all major breeding stock in five Australian states. Two of the heterozygotes were recently imported adult dogs and the others were their offspring. CONCLUSIONS: The frequency of the 107C allele in the Australian population of Irish Setters is lower than that in Europe. Selective breeding programs should be adopted to eliminate the mutant allele presently in two breeding lines.

Alleles↗