Biomedical subjects

G Mullins

Publications and source records attributed to G Mullins.

10 recordsLinked to original sources

PubMed2005

RAGE is the major receptor for the proinflammatory activity of HMGB1 in rodent macrophages.

Abstract High-mobility group box chromosomal protein 1 (HMGB1) is a protein with both intranuclear functions and extracellular cytokine-like effects. In this report, we study possible candidate receptors for HMGB1 on macrophages (Mphi) and define pathways activated by HMGB1 binding. Bone marrow Mphi were prepared from Dark Agouti (DA) rats and stimulated in vitro with HMGB1. The kinetics of tumour necrosis factor (TNF) production, NO production, activation of p38 mitogen-activated protein kinase (MAPK), p44/42 MAPK- and SAPK/JNK-signalling pathways, nuclear translocation of nuclear factor kappa B (NF-kappaB) and HMGB1-induced upregulation of major histocompatibility complex (MHC) class II and CD86 were analysed. Mphi from interleukin (IL)-1 receptor type I-/-, Toll-like receptor 2 (TLR2-/-) and RAGE-/- mice were used to investigate the role of these receptors in HMGB1 signalling. HMGB1 induced TNF and NO production by Mphi, phosphorylation of all investigated MAP kinase pathways and NF-kappaB translocation, and expression of MHC class II was increased. Mphi from RAGE-/- mice produced significantly lower amounts of TNF, IL-1beta and IL-6, while IL-1RI-/- and TLR2-/- Mphi produced cytokine levels comparable with wildtype controls in response to HMGB1 stimulation. We conclude that HMGB1 has the potential to induce a proinflammatory phenotype in Mphi, with RAGE as the major activation-inducing receptor.

Animals↗

PubMed2004

Interleukin-2, interferon-alpha and 5-fluorouracil immunotherapy for metastatic renal cell carcinoma: the all Ireland experience.

OBJECTIVE: To analyse the long-term efficacy of combined interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) subcutaneously, with 5-fluorouracil (5-FU) intravenously in a general multicentre setting, as treatment for metastatic renal cell carcinoma (RCC). METHODS: Fifty-nine patients with metastatic RCC were scheduled to receive an 8-week cycle of immunotherapy. Karnofsky score ranged from 70 to 100 (median 90). Thirty-one patients at presentation had metastases of which 14 underwent nephrectomy. Metastases occurred in multiple organs (lung 74%, mediastinal lymphadenopathy 22%, bone 21%). Therapeutic response and survival were analysed. RESULTS: Nine patients died from disease progression prior to completion of one full cycle. Six cases (10%) have stable disease at a follow-up of 51 months (range 20-88 months). Currently 11 patients (19%) are alive at a mean follow-up of 45 months (range 18-88 months). Forty-eight patients (81%) died of their disease at a mean follow-up of 10 months (range 0.5-46 months). Survival rate at 1 year was 53%, at 2 years 21%, at 3 years 16% and at 5 years 5%. Overall median survival is 10 months. CONCLUSION: IL-2 and IFN-alpha with 5-FU based immunotherapy achieve durable survival rates at 3 years in a minority of patients. Addition of 5-FU does not increase survival in our group. This study population is very different to other reported series. However it reflects better the entire population with metastatic RCC though results are subsequently poorer. Identifying patients that will respond is paramount.

Adult↗

PubMed2000

Combined subcutaneous recombinant alpha-interferon and interleukin-2 in metastatic renal cell cancer: results of the Multicentre All Ireland Immunotherapy Study Group.

OBJECTIVE: To analyse the toxicity and efficacy of combined interferon-alpha and interleukin-2, administered subcutaneously in a general multicentre setting, as treatment for metastatic renal cell carcinoma. METHODS: Thirty-three patients with metastatic renal cell carcinoma were scheduled to receive 2 cyclical doses of subcutaneous interferon-alpha (week 1: 5 MU x 3 days) and interleukin-2 (week 2: 36 MU x 2 days, 9 MU x 3 days; weeks 3-5: 9 MU daily). Karnofsky scores ranged from 80 to 100 (median 90). Metastases occurred in multiple organs (lung 63%, retroperitoneal 39%, liver 24%). Patients were categorised according to the risk of disease progression. Treatment toxicity, therapeutic response and actuarial survival were analysed. RESULTS: All patients received recommended doses of treatment, but 6 received less than 2 cycles. Most were treated as outpatients, although hospitalisation was usual during the 1st week of a cycle. All complained of mild flu-like symptoms. Severe side effects developed in 13 patients (39%), and treatment was discontinued in 3 of these patients. No deaths occurred as a result of treatment. The overall median survival was 10 months. The overall actuarial survival rate at 3 years was 22%. On statistical analysis, actuarial survival rates were not influenced by either response to treatment or risk group category. CONCLUSION: Subcutaneously administered, combined interferon-alpha and interleukin-2 therapy achieves durable survival rates in a minority of patients with renal cell carcinoma. Toxicity is remedial, and not fatal, when subcutaneous therapy is administered by multiple medical disciplines at a variety of centres.

Carcinoma, Renal Cell↗

PubMed1999

Self-assessment in a problem-based learning curriculum in dentistry.

The creation of sound self-judgement for students is an integral goal in any educational sphere. Student clinicians in dentistry must learn sufficient skills to be able to self-assess their performance very accurately, because after graduation, the nature of dental procedures means that others are seldom in a position to evaluate the quality of their work. Over recent years, the Department of Dentistry at the University of Adelaide has been developing a self-assessment procedure, initially as a pilot study in the subject oral diagnosis, and currently in all years of the course. This paper describes how self-assessment has been demonstrated to work initially in the pilot subject, and currently across the whole course. The paper also describes how the criteria for assessment and the levels of performance expected for each grade are established and how student performance is monitored. Finally, evidence is presented to indicate acceptance by the students of self-assessment as a valuable and integral part of their learning in dentistry.

Curriculum↗

PubMed1996

The use of student journals in problem-based learning.

This paper describes several examples of the use of journals in a Bachelor of Dental Surgery course. The examples cover: the use of journals in first year subjects and in later-year clinical subjects; the effect of changes in policy and practise as a result of experience with journals; and student views on their experiences with journals. The use of journals offers a means of achieving some of the more important goals of problem-based learning (PBL), particularly those requiring students to reflect upon and evaluate their experiences. When effectively integrated in a PBL course, journals have several functions: to formalize reflection; an outlet for personal feeling; an opportunity for feedback about a student's progress and about the course; to provide the student with a summary of the year's work; and a means whereby students and teachers gain insight into the learning process. However, our experience in Dentistry raises several contentious issues, especially with regard to confidentiality and assessment. We make several recommendations for the effective use of journals based on the need for frequent communication between students and staff, the development of an environment of trust, and the need for staff and student education in journal use.

Adult↗

PubMed1996

First-year responses to a new problem-based curriculum in dentistry.

The first year of a new Bachelor of Dental Surgery curriculum was introduced at the University of Adelaide in 1993. Four integrated streams replaced the previous large number of separate subjects, with an overall reduction in formal contact hours, more exposure to clinical practise, and an emphasis on problem-based learning and student self-directed learning. This report compares students attitudes to the new programme with their attitudes to the previous course. Evaluation forms were completed by 30 of 53 first-year students in 1992 and 38 of 47 first-year students in 1993. Comparisons between years, made using the Student's that, indicated significant differences for several questions. For example, the workload in the previous course was considered to be significantly heavier, with too much theory and too many topics. It was felt that the aims and objectives of the new course were significantly clearer; there was more time to understand material; more opportunities to choose areas to study; students were encouraged more to think for themselves; and staff were more understanding and supportive. The authors conclude that the new problem-based Adelaide dental curriculum has facilitated a more contextual and better-balanced learning environment for students.

Attitude↗

PubMed1995

Assessing the economic impact of immunisation against East Coast fever: a case study in coast province, Kenya.

The cost of immunising cattle against East Coast fever by the infection and treatment method has been calculated for a pilot scheme in Kaloleni Division of the Coast Province of Kenya by using a spreadsheet model. The cost was calculated to be KSh 544 (US$25) per animal (in 1990 values). If a farmer were to bear all this cost, immunisation would be financially profitable in grade cattle, but the benefits of immunisation would not be sufficient to justify the immunisation of zebu cattle. For these animals, the cost of immunisation would have to be in the range of KSh 230 to KSh 415 per animal, or the farm-gate price of milk would have to increase by at least 80 per cent from KSh 7.50 to 13.50/litre, or the government would have to subsidise the cost either partially or fully. The first two possibilities are realistic, because the costs of routine immunisation are likely to be lower than for the pilot scheme, and because the increasing demand for milk is likely to push up prices in the liberalised markets. If both the grade and zebu cattle in Kaloleni Division were targets for immunisation, it is estimated that there would be 14,500 head for immunisation annually, costing an estimated KSh 8 million. The spreadsheet model used to assess the economics of immunisation in the Kaloleni Division could be applied to determine the government or private veterinary service charges for immunisation that would be financially profitable to farmers in a defined cattle production system in any division, district or country. The model could also be used to estimate the annual total number of cattle for immunisation in a target cattle production system and thus help with the financial planning for the exercise.

Animals↗

PubMed1994

A problem-based approach to a course in oral diagnosis.

This paper describes the first two years of an attempt to introduce a problem-based approach into the teaching of oral diagnosis. The most significant features of this approach were the involvement of the students in setting course goals, the use of student journals to encourage reflection on learning, the encouragement of self-assessment, and an attempt to relate clinical practice to problem-solving seminars. The paper reports on student reactions to the course and discusses further developments in the course, in particular attempts to develop a more explicit understanding in students of their own learning processes, and more attention to factors in the learning environment which engender confidence, reflection and self-evaluation.

Diagnosis, Oral↗

PubMed1988

Nosocomial infections in a pediatric intensive care unit.

In a prospective 30-month study of nosocomial infections in a pediatric ICU (PICU), the incidence, sites, and causes of infection were determined. Factors associated with increased risk of infection were investigated. In 1,388 patients who remained in the PICU for a minimum of 72 h, 116 infections occurred (6.1 infections/100 admissions). Primary bacteremias comprised 38% of PICU infections and lower respiratory infections comprised 15%. The remaining infections were divided equally among GI, skin, eye, upper respiratory, postoperative wounds, and other sites. Coagulase-negative staphylococci, Pseudomonas aeruginosa, and Staphylococcus aureus were the most prevalent pathogens. Surgical patients had similar rates of infection to medical patients. Patients in the first 2 yr of life, particularly those between 7 and 30 days of age, had the highest rate of infection. Onset of infection was more common after the first week in the PICU with 11% of patients staying 14 to 20 days, 27% of patients staying 21 to 27 days, 48% of patients staying 28 to 34 days, and 52% of patients staying more than 35 days before the onset of infection. The risk of nosocomial infection increases with arterial and central line use, prolonged intubation, ventilation, intracranial pressure monitoring, and paralysis.

Age Factors↗

PubMedDate not supplied

Aggressive management leads to improved survival in patients with small cell lung carcinoma.

BACKGROUND: Small cell lung carcinoma (SCLC) accounts for 17-25% of all cases of lung cancer, and remains the most lethal form of this disease. AIMS: We sought to determine whether an aggressive treatment policy led to an increase in median survival in patients with SCLC in our institution. METHODS: From 1985 to 1993, patients with SCLC were often treated conservatively on the basis of advanced age or poor performance status. From 1993 to 1998, a more aggressive management policy was adopted. All patients were treated with chemotherapy. Radiotherapy was administered, where appropriate, following the completion of chemotherapy. The medical records of 66 patients were analysed and clinical outcomes were compared. RESULTS: Median survival in the 1993-98 group (332 days) was significantly better compared to the 1985-93 group (194 days) (p = 0.02). In patients with limited disease, median survival in the 1993-98 group (489 days) was also significantly better compared to the 1985-93 group (254 days) (p = 0.04). The difference in median survival in extensive disease was not significant (p = 0.09). CONCLUSIONS: The presented data suggest that appropriate aggressive management of patients with SCLC leads to a significant increase in median survival. This survival benefit is most apparent in patients with limited disease.

Aged↗