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Biomedical subjects

A O'Callaghan

Publications and source records attributed to A O'Callaghan.

9 recordsLinked to original sources
PubMed2006

Treatment of sepsis: current status of clinical immunotherapy.

While antibiotics address the root cause of sepsis--that of pathogen infection--they fail to provide an adequate cure for the condition. Currently, 30% to 50% of septic patients die, and this figure is likely to increase in line with the proliferation of multi-drug resistant bacteria. With an increased understanding of the immune response, it has been proposed that modulation of this defence mechanism offers the best hope of cure. Many entry-points in the immune system have been identified and targeted therapies have been developed,but why are these not in routine clinical practice? This review examines the latest evidence for the use of immuno-modulating drugs, obtained from human clinical trials. We discuss cytokine-based therapies, steroids and anti-coagulants. Finally, consideration is given as to why successful therapies in the laboratory, and in vivo models, do not automatically translate into clinical benefit

Animals↗
PubMed2004

Effect of gluten-free diet and adherence on growth and diabetic control in diabetics with coeliac disease.

AIMS: To study the effect of gluten-free diet on growth and diabetic control of children with type 1 diabetes mellitus and coeliac disease. METHODS: Twenty one children (mean age 7.5 years, range 1.6-12.9) with type 1 diabetes, primarily initially identified on the basis of symptoms and consecutively diagnosed with coeliac disease by biopsy over a 10 year period, were matched by sex, age at onset, and duration of diabetes with two diabetic controls without coeliac disease. Weight, height, haemoglobin A1c, and insulin requirements were measured before and for 12 months after the diagnosis and treatment of coeliac disease. Dietary awareness and adherence were assessed by structured questionnaire. RESULTS: A gluten-free diet resulted in a significant increase in weight-for-age z scores at 12 months after diagnosis (mean increase in z score 0.33) and in BMI (mean increase in z score 0.32). Increases in height did not achieve statistical significance. Controls showed no significant changes in weight, height, or BMI over the same period. Insulin dosage at diagnosis was less in coeliacs than in controls (mean difference 0.16 units/kg/day), but was similar to controls once a gluten-free diet had been established. Questionnaires were obtained in 20 patients. There appeared to be a relation between dietary awareness/adherence and growth parameters, but the small number of patients with "poor/fair" dietary adherence prevented meaningful analysis of this group. CONCLUSION: Identification and dietary treatment of coeliac disease in children with diabetes improved growth and influenced diabetic control. Evaluation of the outcome of treatment of coeliac disease in diabetics should include assessments of gluten intake.

Analysis of Variance↗
PubMed2003

Combination chemotherapy in advanced gastrointestinal cancers: ex vivo sensitivity to gemcitabine and mitomycin C.

Advanced or metastatic disease is common in both oesophagogastric and colorectal cancers, with poor 5-year survival despite palliative chemotherapy. We have investigated the sensitivity of gastrointestinal tumours to gemcitabine in combination with mitomycin C (GeM), using a modified ex vivo ATP-based tumour chemosensitivity assay (ATP-TCA). Tumour material from 41 colorectal and 22 oesophagogastric cancers were assessed. The GeM combination showed variable but definite activity in most of the samples tested. The results show that GeM achieves >95% inhibition at concentrations within the range achievable clinically in 60% of colorectal tumours (21 out of 35) and 38% of oesophagogastric tumours (five out of 13) tested. We did not identify any significant difference in sensitivity using concurrent or sequential exposure of tumour-derived cells to these two drugs. The results from this study suggest that GeM may be a useful combination in the treatment of advanced gastrointestinal malignancy.

Adult↗
PubMed1997

PACE BOM chemotherapy: a 12-week regimen for advanced Hodgkin's disease.

BACKGROUND: This study was designed to evaluate the efficacy and toxicity of a 12-week alternating weekly chemotherapy regimen for advanced Hodgkin's disease. Consolidative irradiation of residual masses was used in selected cases. PATIENTS AND METHODS: Eighty-three patients with newly diagnosed advanced Hodgkin's disease (bulky stage IIA, stage IIB-IVB) or with progressive disease after extended field radiotherapy for early stage disease were included in this study. The patients were treated for 12 weeks with PACE BOM comprising oral prednisolone together with intravenous doxorubicin, cyclophosphamide and etoposide alternating weekly with intravenous bleomycin, vincristine and methotrexate. Limited field adjuvant radiotherapy was also given to 21 patients with localised persistent radiological abnormalities visible on chest X-ray after chemotherapy. The study end points were overall survival, failure free survival (FFS) and toxicity, particularly with respect to reproductive function. RESULTS: With a median post treatment follow up of 52 months the actuarial 5-year overall survival is 90% (confidence interval 81%-95%) and FFS is 64% (52%-74%). This treatment was well tolerated and fertility was maintained in a high proportion of young adults. CONCLUSIONS: The brief duration PACE BOM regimen with or without radiotherapy appears to be comparable in efficacy to other doxorubicin containing regimens, with a favourable toxicity profile. Randomised clinical trials are now needed to evaluate the role of this and comparable initial treatment approaches to advanced Hodgkin's disease.

Adolescent↗
PubMed1997

Testicular carcinoma.

Testicular cancer is the commonest malignancy in young males and its incidence has more than doubled in the last 25 years. For clinical purposes, two tumour types are identified, seminoma and non-seminoma germ cell tumours (loosely known as teratomas). Stage I disease is confined to the testes and is managed surgically, with adjuvant chemotherapy or radiotherapy as appropriate. Cisplatin-based chemotherapy is the cornerstone of treatment for metastatic disease, with cure rates exceeding 80%. Early diagnosis and cure should be the aim in all patients. To this end, those with testicular symptoms should be evaluated promptly by ultrasound, and in young male patients presenting with the clinical picture of metastatic disease, germ cell tumour should top the list of differential diagnoses.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Single-fiber study of contractile and biochemical properties of skeletal muscles in streptozotocin-induced diabetic rats.

Mechanically skinned, single muscle fibers, isometrically activated in pH and Ca2+ (Sr2+) buffered solutions were used to examine the function of the contractile apparatus in slow- and fast-twitch fibers from soleus (SOL, predominantly slow-twitch) and extensor digitorum longus (EDL, predominantly fast-twitch) muscles of streptozotocin (STZ)-induced diabetic rats and age-matched controls. Three and 14 days after STZ administration, the contractile properties of muscle fibers from diabetic rats did not differ significantly from those of controls with respect to several mechanical parameters, such as maximum Ca-activated tension, activation threshold, and sensitivity to Ca2+ and Sr2+. In contrast, 28 days after STZ administration, 37.5% of the fast-twitch EDL fibers developed maximum activated tensions (77.1 +/- 10.4 kN/m2), which were significantly lower than those developed by controls (244.0 +/- 14.3 kN/m2), and the slow-twitch SOL fibers displayed a significantly higher sensitivity to Ca2+ (and Sr2+) than the controls. All fibers from diabetic rats, including the low-tension EDL fibers and higher Ca sensitivity SOL fibers displayed control-like electrophoretic profiles of the major myofibrillar proteins. Taken together with data from earlier studies on the effects of long-term diabetes on whole skeletal muscle contractility, these results strongly suggest that 1) the decrease in tetanic tension output of EDL muscles induced by diabetes is caused mainly by direct effects of the diabetic condition on the contractile/regulatory system of a subpopulation of fast-twitch fibers, which develop little force, and 2) the diabetes-induced slowing of twitch times of SOL muscles is caused in part by the increased sensitivity to Ca2+ of the contractile apparatus in the slow-twitch fibers.

Analysis of Variance↗