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Biomedical subjects

C Fegan

Publications and source records attributed to C Fegan.

29 records · Page 2Linked to original sources

Antigenaemia during acute graft versus host disease.

AIMS: Animal studies have shown that antigens present within the gut play an important role in the development of acute graft versus host disease (GvHD) following allogeneic bone marrow transplantation (BMT). In previous studies, inert sugars have been found to penetrate the small bowel mucosa after conditioning therapy for BMT; endotoxaemia can also occur during acute GvHD. Data on absorption of antigenic proteins across the gut following BMT in humans have not been presented as yet. METHODS: Six patients undergoing allogeneic BMT were studied to determine whether enteric ovalbumin absorption increased or endotoxaemia developed during acute GvHD. RESULTS: Three patients had minimal antigenaemia and no detectable endotoxaemia before receiving conditioning therapy. At the onset of acute GvHD, however, much higher ovalbumin concentrations were detected in those patients with severe antigenaemia. Serum concentrations of specific antiovalbumin IgG and IgA, or antiendotoxin IgM or IgG had no bearing on detectable IgG or IgM ovalbumin or endotoxin concentrations. In five of six patients, small bowel permeability increased, as tested by the lactulose/mannitol sugar absorption test, but detectable ovalbumin absorption increased in only three of these and only two developed endotoxaemia. CONCLUSIONS: Antigens present within the gut can cross the mucosal epithelium during acute GvHD, probably resulting in an enhanced immune response.

Acute Disease↗

In vitro LAK (lymphokine activated killer) activity following autologous peripheral blood stem cell is significantly greater than that following autologous bone marrow and allogeneic bone marrow transplantation.

LAK activity is known to increase following autologous and allogeneic bone marrow transplant and peripheral blood stem cell transplant (PBSCT). The aim of this study was to directly compare the 3 types of transplant and the LAK activity generated. LAK activity following PBSCT is significantly greater than that following autologous bone marrow transplantation and even allogeneic transplantation up to 8 weeks. The type of killer cells generated is similar for the different types of transplants, with most killing activity following PBSCT due to CD56+ cells, though CD3+ cells also contribute. This study would suggest that attempts to augment the graft-versus-leukaemia effect is more likely to be successful following PBSCT than autologous bone marrow transplantation.

Adolescent↗

Karyotypic evolution in CLL: identification of a new sub-group of patients with deletions of 11q and advanced or progressive disease.

Chronic lymphatic leukaemia (CLL) is the most common leukaemia and is characterized by long-term survival. Previous studies have shown that karyotypic abnormalities are relatively stable and that certain abnormalities may be associated with a poor prognosis. In a prospective 5-year study of 45 patients with typical CLL, sequential karyotypic studies were undertaken every 6-12 months. Clonal karyotypic abnormalities were identified in 62% of patients, either at diagnosis or during the study period with 38% (17/45) exhibiting clonal evolution. In patients with no clinical disease progression, 13q abnormalities were most commonly detected compared with 11q deletions in patients with progressive disease. Karyotypic evolution was significantly associated with progressive disease (12/16, 75% vs 5/29, 17%; P < 0.001, chi2). Thus, karyotypic evolution is not uncommon in CLL, is usually associated with disease progression and deletions of 11q are the commonest detected abnormalities.

Adult↗

Effect of IgM-enriched intravenous immunoglobulin (Pentaglobin) on endotoxaemia and anti-endotoxin antibodies in bone marrow transplantation.

Endotoxin was measured in over 1000 plasma samples from bone marrow transplant patients in a randomized trial of the IgM-enriched intravenous immunoglobulin (IVIG) Pentaglobin. Peak endotoxaemia was significantly reduced (P = 0.02) in patients receiving Pentaglobin and 70% of all pyrexias of unknown origin were associated with endotoxaemia. Gut mucosal damage, assessed by lactulose/mannitol ratios, was significantly associated (P = 0.02) with endotoxaemia. Specific IgM antibody to endotoxin core-glycolipid was significantly raised (P < 0.01) in patients receiving the IVIG, and the IgM fraction of Pentaglobin was found to contain most of the anti-endotoxin antibody activity of the IVIG. These results suggest a role for IgM-enriched IVIG as a prophylactic agent for the reduction of endotoxaemia and its consequences in bone marrow transplant patients.

Adolescent↗

Use of IgM enriched intravenous immunoglobulin (Pentaglobin) in bone marrow transplantation.

In a study of 63 allogeneic and autologous bone marrow transplants, patients were randomized to receive the IgM and IgA enriched intravenous immunoglobulin (IVIG) preparation (Pentaglobin). Pentaglobin has been postulated to have anti-endotoxin properties and one of the aims of the study was to measure endotoxin levels in these patients together with the clinical sequelae of infection. The anti-endotoxin effects of Pentaglobin were found to reside in the IgM fraction. Those patients who received Pentaglobin were significantly protected from dying from infection in the first 100 days after the transplant, although it was not actually possible to document bacterial infections as the cause of death in the control patients. Peak endotoxin levels were significantly reduced (p = 0.02) in those patients receiving Pentaglobin. Liver damage as assessed by liver enzyme abnormalities correlated significantly with the presence of endotoxaemia greater than 25 pg/ml and up to 70% of pyrexial episodes were associated with endotoxaemia. Our results suggest that Pentaglobin is useful in reducing hepatic toxicity and this may be related to a reduction in endotoxaemia.

Adolescent↗

The gut mucosal barrier in bone marrow transplantation.

The damage to the small bowel mucosal barrier was studied prospectively in 26 patients undergoing bone marrow transplantation. The conditioning regimens resulted in the small bowel mucosa becoming more permeable for up to 4 weeks. Acute graft-versus-host disease also compromised barrier function. There was no difference in gut damage between conditioning with chemotherapy only and chemoradiotherapy, but damage was greater in patients 30 years of age and above.

Acute Disease↗

Pulmonary infection with Nocardia caviae in a patient with diabetes mellitus and liver cirrhosis.

The first reported case of pulmonary infection with Nocardia caviae in Britain occurred in a 67 year old woman, in whom diabetes mellitus and liver cirrhosis probably contributed to impaired cell mediated immunity. She was successfully treated with gentamicin 60 mg eight hourly and sulphadimidine 500 mg six hourly for six months and then with sulphadimidine 2 g/day for a further three months. When Nocardia caviae is isolated from the sputum of a patient with chronic respiratory infection and fever, effective treatment should be started promptly.

Aged↗