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Biomedical subjects

S R McCann

Publications and source records attributed to S R McCann.

At least 73 records · Page 4Linked to original sources

Inhibitory effect of cyclosporin A on erythroid and stromal colonies.

Cyclosporin A is used to prevent graft-versus-host disease (GvHD) following bone marrow transplantation (BMT) and it has been implicated in reducing the time to engraftment for leukaemia and aplastic anaemia patients. To evaluate the effect of cyclosporin A on engraftment, the proliferative capacity of bone marrow progenitors (CFU-E, CFU-F and CFU-C) was assessed both in vitro and following treatment with cyclosporin A over a 9-week period using an animal model. Cyclosporin had a differential effect on the haemopoietic progenitors, with the myeloid series unaffected at therapeutic concentrations. Both erythroid and stromal progenitors were significantly inhibited at similar concentrations. The mechanism by which cyclosporin A enhances engraftment remains unclear; however, it is not mediated by enhancing any of the haemopoietic progenitors.

Administration, Oral↗

Persistent polyclonal B lymphocytosis with Epstein-Barr virus antibodies and subsequent malignant pulmonary blastoma.

Persistent polyclonal B lymphocytosis (PPBL), a rare benign lymphoproliferative disorder, occurred in a 25 year old woman. The lymphocytes showed the phenotype cIgM+, FMC7+, CD19+, CD20+, which was similar to that seen in Waldenstrom's macroglobinaemia, but the proliferation was repeatedly shown to be polyclonal both immunologically and by immunoglobulin gene rearrangement studies. Eleven years after presentation the patient developed a malignant pulmonary blastoma, a rare pulmonary tumour of combined epithelial and mesenchymal origin. The failure to develop a lymphoid malignancy over 11 years together with immunological and genetic evidence of polyclonality confirms that PPBL is a benign lymphoproliferative disorder. The subsequent occurrence of a nonhaemopoietic malignancy suggests that benign lymphoid proliferations, like their malignant counterparts, may predispose to the development of neoplasia. A role for Epstein-Barr virus in the pathogenesis of one or both of these rare conditions is suggested by the finding of raised Epstein-Barr viral capsid antigen titres.

Adult↗

Early detection of leukaemic relapse after bone marrow transplantation using the polymerase chain reaction.

We report a case of acute lymphoblastic leukaemia relapsing after allogeneic bone marrow transplantation in which the polymerase chain reaction (PCR) was used to assess chimeric status. This technique demonstrated the progressive reappearance of host cells prior to clinical relapse. The relapse was of host cell origin as shown by the presence of female (recipient) metaphases containing an abnormal chromosomal marker (iso 9q) which had also been present at initial diagnosis. The emergence of host cells in this case, detected only by PCR techniques but not by cytogenetic methods, appeared to herald overt relapse. PCR analysis provides a sensitive tool for detecting a progressive rise in host cell numbers which may predict clinical relapse.

Adult↗

The value of the erythrocyte indices as a screening procedure in predicting nutritional deficiencies.

The results of a large number of nutritional screen requests (n = 871) were compared with corresponding values of erythrocyte indices considered predictive of nutritional deficiencies to determine if such indices could be used in a prospective screening procedure to restrict the number of serum vitamin B12, folate, and ferritin assays. Low mean cell haemoglobins (MCH less than 27 pg) were found to be superior to low mean cell volumes (MCV less than 77 fl), in predicting low serum ferritin values. The occurrence of deficient ferritin values was 90% when the MCH was very low (MCH less than 23 pg). Vitamin B12 or folate deficiency could not be predicted from the MCV. A normal MCV was found in more than 55% of vitamin B12 deficient samples and some 30% of serum B12 deficients (less than 150 micrograms/l) showed no evidence of anaemia (Hb greater than 12 gm/dl) or macrocytosis (MCV less than 100 fl). It would not seem appropriate to use erythrocyte indices alone as a method of selecting samples for further investigation of folate or vitamin B12 status.

Adult↗

Nebulized amphotericin B as prophylaxis against invasive aspergillosis in granulocytopenic patients.

The efficacy of inhaled amphotericin B in prevention of invasive aspergillosis in patients with granulocytopenia (granulocytes less than 0.5 X 10(9)/l for greater than 10 days) was investigated over a 12-month period. Amphotericin B prophylaxis was administered twice daily for the period of granulocytopenia to 34 patients who were at risk during 144 episodes of granulocytopenia. The cohort at risk was compared with historical controls. In the 2 years prior to institution of prophylaxis, 14 patients (11.4% of those at risk) developed invasive aspergillosis. All cases occurred whilst the patients were nursed on the open wards. Aspergillosis did not develop in 25 granulocytopenic patients nursed in single rooms with HEPA filtration. Since institution of prophylaxis, there have been no cases of invasive aspergillosis. These data suggest that nebulized amphotericin B may be useful in preventing invasive pulmonary aspergillosis in granulocytopenic patients, especially those nursed on the open wards, and warrants further investigation.

Agranulocytosis↗

Pulmonary disease following allogeneic bone marrow transplantation.

Bone marrow transplantation is the treatment of choice of many haematological disorders but its success is limited by two major complications, graft-versus-host disease (GVHD) and pulmonary disorders. Of the first 31 patients transplanted at St. James's Hospital (1984-1986) 16 (52%) had a successful outcome. Of the 15 patients who died, two died of GVHD and one of recurrent leukaemia. All others had severe pulmonary disease either causing death directly (9 cases) or contributing to death from toxic encephalopathy, carditis or recurrent leukaemia (1 case each). The principal forms of pulmonary disease were cytomegalovirus pneumonitis (4 cases), acute haemorrhagic pulmonary oedema (4 cases) and pneumocystis carinii pneumonia (2 cases). There were single cases of staphylococcal pneumonia and idiopathic pulmonary fibrosis. Aspergillus was a second pathogen in two cases. Pulmonary damage due to conditioning chemoradiotherapy and to GVHD probably underlies this high incidence of pulmonary disease. T-cell depletion to limit the incidence of GVHD together with increased prophylaxis against CMV and pneumocystis carinii will probably substantially reduce these complications in the near future.

Adolescent↗

Enterobacter cloacae in a haematology/oncology ward--first impressions.

The observation that Enterobacter cloacae has emerged as a cause of infection in a haematology/oncology ward prompted a prospective study over an eight-month period. Sensitivity to antibiotics, plasmid screening and typing methods were used to describe the epidemiology of the organism which was isolated from 22 patients. There was evidence of a limited amount of cross infection. No common sources were found. A large number of distinct strains were identified. E. cloacae infection was associated with prolonged profound leucopenia and broad-spectrum antibiotic therapy.

Adolescent↗

Chimaerism following allogeneic bone marrow transplantation: detection of residual host cells using the polymerase chain reaction.

Chimaerism was assessed in five recipients following sex mismatched allogeneic bone marrow transplantation. Techniques included karyotyping of bone marrow cells, dot blot DNA analysis of blood and bone marrow suspensions, and in vitro amplification of DNA by the polymerase chain reaction (PCR) using blood and bone marrow suspensions and stored bone marrow slides. Results of karyotypic analysis suggested complete chimaerism in four patients, while in one patient mixed chimaerism was detected. Mixed chimaerism was also detected, however, in a second patient using PCR and confirmed by dot blot analysis on all tissues examined. PCR is a sensitive tool for investigation of chimaerism following bone marrow transplantation. Since this technique does not require radioactivity, it is an attractive method for use in a clinical laboratory. This technique represents a further development in the use of DNA methodologies in the assessment of haematological disease.

Blotting, Southern↗

A comparison between regimens containing chemotherapy alone (busulfan and cyclophosphamide) and chemotherapy (V. RAPID) plus total body irradiation on marrow engraftment following allogeneic bone marrow transplantation.

The effect of two conditioning regimens given prior to allogeneic bone marrow transplantation (BMT) on the kinetics of engraftment were compared. 5 patients received busulfan and cyclophosphamide: 7 patients received daunorubicin, vincristine, cytosine arabinoside, methylprednisone and VM-26 plus total body irradiation (TBI). Bone marrow progenitors (BFU-E, CFU-E, CFU-GM, CFU-F) were assayed up to 3 months post-BMT. All progenitors were severely depressed in spite of peripheral blood recovery. There was no stromal recovery in any adult patient post-BMT. There was no significant difference in time to engraftment, or colony forming units, or between patients conditioned with chemotherapy alone or chemotherapy plus TBI. We were unable to detect effects of graft-versus-host disease or cytomegalic viral infection on bone marrow progenitors or peripheral blood recovery in this study.

Bone Marrow↗

Iron deficiency in pre-menopausal females.

Of 20 women (pre-menopausal) with iron deficiency anaemia, only three felt that their periods were unduly heavy. However, on objective assessment of menstrual loss using the alkaline haematin method, the blood was found to be excessively heavy in 12 cases (296 +/- 45 mls per cycle: normal is 80 mls/cycle). The findings emphasise that women underestimate the extent of menorrhagia.

Adolescent↗

Value of surveillance cultures in the management of neutropenic patients.

To assess whether bacteriological surveillance cultures can be used to predict infection in neutropenic patients, cultures were performed during the period of neutropenia of nose, throat and urine specimens collected once weekly and faeces specimens collected twice weekly. Seventy-six consecutively observed patients undergoing chemotherapy for haematological or non-haematological diseases were investigated. Severe infection including septicaemia, lower respiratory tract infection, anorectal lesion and urinary tract infection occurred in 32 patients. Enterobacter cloacae, Escherichia coli and Pseudomonas aeruginosa were the organisms most commonly involved. In the majority of cases of septicaemia the organisms were isolated from the faeces, often in pure culture, prior to the onset of septicaemia. Most of the isolates of Enterobacter cloacae were resistant to the empiric antibiotic therapy used in the unit and were able to colonise multiple sites, presumably increasing the risk of subsequent infection. Faecal culture is the most useful approach in bacteriological surveillance in neutropenic patients.

Adolescent↗