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Biomedical subjects

I M Hann

Publications and source records attributed to I M Hann.

At least 73 records · Page 4Linked to original sources
PubMed1989

Serratia marcescens outbreak in a paediatric oncology unit traced to contaminated chlorhexidine.

Over an 18-month period we encountered 12 episodes of Serratia marcescens bacteraemia in 10 patients in a paediatric oncology unit. These were associated with long-term indwelling Hickman intravenous catheters (right atrial) and caused three deaths. Seven of the patients had only mild pyrexial illnesses and made a complete recovery. The source was traced to contaminated aqueous chlorhexidine in a bedside container in which plastic clamps were stored. When this was rectified the outbreak ceased. The identity of the causal Serratia strains was confirmed by plasmid analysis and they showed multiple antibiotic resistance, including the aminoglycosides. The study illustrates the emergence of S. marcescens as an opportunistic pathogen and emphasises the dangers of Hickman-associated bacteraemia.

Adolescent↗
PubMed1988

A tumour spheroid model for antibody-targeted therapy of micrometastases.

Human neuroblastoma cells grown as tumour spheroids were briefly incubated with a conjugate of 131I and an anti-human neuroectodermal monoclonal antibody UJ13A. Unbound 131I was removed by washing and the spheroids observed in culture conditions for up to 4 weeks. Spheroid response to irradiation was evaluated as time to reach 10x treatment volume and proportion of spheroids sterilised. Spheroid growth was found to be affected by both the activity of 131I-UJ13A and the duration of the incubation. Na[131I], 131I-HSA, 131I labelled non-specific antibody and unlabelled antibody were found to be relatively ineffective compared to 131I-UJ13A. The tumour spheroid model has applications in the evaluation of antibodies or antibody fragments and different radionuclides which may be considered for radioimmunotherapy of micrometastases.

Antibodies, Monoclonal↗
PubMed1988

Blast cell vacuoles in childhood lymphoblastic leukaemia.

As part of a central review of cell morphology in childhood lymphoblastic leukaemia (ALL), marrow smears from entrants to the Medical Research Council trial UKALL VIII, other than those from children with B-ALL, were studied prospectively for the presence or absence of blast cell vacuoles and for any clinical or biological relevance this feature might have. Adequate slides were available from 733 patients (88% of the trial entrants) after five with B ALL were excluded. Vacuolated blast cells (greater than 10%) were present in 204 (28%). The presence of vacuoles was associated with PAS positivity (chi 2 = 27.8; P less than 0.0001), a diagnostic white cell count (WBC) less than 50 x 10(9)/l (chi 2 = 13.1; P less than 0.0001), and the immunophenotype of 'common' ALL (CD10 positive) (chi 2 = 9.1; P less than 0.01). There was no clear association with French-American-British (FAB) type L1 or L2. The 204 patients with vacuoles had a significantly superior disease free survival compared to the remainder (2P = 0.01), a difference which remained significant when the analysis was stratified by FAB type (2P = 0.01), age (2P = 0.02) or sex (2P = 0.02), but which was lost when stratified by WBC (2P = 0.06). These findings provide further evidence that, outside the context of B-ALL, vacuoles are indicative of a relatively benign disease which responds well to therapy. The French-American-British (FAB) classification should be modified to take this into account.

Adolescent↗
PubMed1988

Prevention of graft-versus-host disease by ex vivo T cell depletion: reduction in graft failure with augmented total body irradiation.

Graft-versus-host disease prevention was attempted in 35 consecutive patients with hematological malignancy who received bone marrow from an HLA match sibling donor who was depleted of T cells ex vivo. Five of the first 8 patients who received cyclophosphamide 60 mg/kg on 2 consecutive days followed by fractionated total body irradiation (TBI) (6 x 2 Gy) had graft failure. The subsequent 27 patients had received an extra fraction of TBI (7 x 2 Gy), and only one failed to have stable engraftment. There were no differences in nucleated cell dose, granulocyte-macrophage colony-forming units, or T cell numbers given to the two groups. Neutrophil but not platelet regeneration of those patients who successfully grafted was slower than in a group of historical controls receiving unmanipulated marrow. Significant graft-versus-host disease was prevented with no increase in relapse rate. We suggest that engraftment can be reliably achieved by augmenting the TBI conditioning in recipients of T cell-depleted matched allogeneic bone marrow.

Adolescent↗
PubMed1987

Mortality and morbidity caused by measles in children with malignant disease attending four major treatment centres: a retrospective review.

Measles is a major cause of mortality and morbidity in children receiving treatment for leukaemia. A review was made of all the documented cases of measles in children in first remission from acute lymphoblastic leukaemia at four major treatment centres in 1974-84. Over the 11 years reviewed 1043 children with acute lymphoblastic leukaemia were referred to these centres. Fifty one (4.9%) died while in first remission and 15 (29.4%) of these deaths were due to measles or its complications: 12 cases of pneumonia, 10 of them fatal; and six cases of encephalitis, five of them fatal and the sixth child left severely handicapped. These children would have had at least a 50% chance of long term survival. The severity of measles in the immunocompromised patient reinforces the need to improve the poor uptake of measles immunisation in Britain.

Acute Disease↗
PubMed1987

Scottish validation study of Cancer Registration data childhood leukaemia 1968-1981. Bone marrow review--II.

Following a review of central leukaemia registration data for Scottish children 1968-1981 a retrospective assessment of leukaemia type was made by inspection of bone marrow slides. Only 57% of slides were still available and in 72% of these the review panel confirmed the initial diagnosis of leukaemia and its type. In eight cases the panel disagreed with the diagnosis or the type of leukaemia designated. Central slide review at diagnosis in childhood leukaemia is essential if subsequent epidemiological studies are to be meaningful.

Adolescent↗
PubMed1987

The effect on human neuroblastoma spheroids of fractionated radiation regimes calculated to be equivalent for damage to late responding normal tissues.

Multicellular tumour spheroids (MTS) are a useful in vitro model of human cancer. An experiment was designed to assess the likely therapeutic advantage of hyperfractionation--a proposed strategy in radiotherapy. A cell line (NB1-G) derived from human neuroblastoma was grown as MTS. This MTS line is radiosensitive with low capacity for repair of sublethal radiation damage. These properties make NB1-G a suitable line to test the theoretical advantage of hyperfractionation. MTS were irradiated using alternative fractionated regimens, with fraction sizes varying from 0.5 to 4 Gy. In each experiment, the total dose was chosen to make the regimens theoretically isoeffective for damage to late-responding normal tissues (calculated using the linear-quadratic mathematical model with alpha/beta = 3 Gy). The radiation responses of MTS were evaluated using the end-points of regrowth delay and "proportion cured". Regimens using smaller doses per fraction were found to be markedly more effective in causing damage to neuroblastoma MTS, as assessed by either end-point. These experimental findings support the proposal that hyperfractionation should be a therapeutically advantageous strategy in the treatment of tumours whose radiobiological properties are similar to those of the MTS neuroblastoma line NB1-G.

Cell Line↗
PubMed1987

Bone marrow necrosis in acute lymphoblastic leukaemia.

Bone marrow necrosis, an uncommon finding in acute lymphoblastic leukaemia, has previously been regarded as a poor prognostic feature. It has been associated with difficulty in establishing the diagnosis, a low rate of remission as well as short remission duration. We report a case of bone marrow necrosis in a girl with acute lymphoblastic leukaemia and good prognostic features who attained complete remission uneventfully and will discuss previous reports of this association in the literature.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

The clinical significance of blast cell morphology in childhood lymphoblastic leukaemia.

The morphological classification of ALL based on the FAB co-operative group's criteria is capable of identifying 10-15% of children with L2 disease who, given similar treatment, will fare less well than the 85-90% with the L1 variant. The significant features defining L2 morphology are a low cellular nuclear: cytoplasmic ratio and the presence of nucleoli. Children with L2 disease do not have higher leucocyte counts but are older, have "common" ALL less frequently, and more often have well-preserved marrow function at diagnosis. Their poor outlook is manifest not only by their higher relapse rate but also by a higher proportion failing to remit in the first instance. L2 morphology does not necessarily "breed true" and can arise in a small proportion of patients with previous L1 disease at the time of relapse. Other striking morphological features of lymphoblasts, including azurophil granules, vacuoles and "hand mirror" cells, have yet to have their significance defined, though the latter feature may be an unfavourable finding.

Child↗
PubMed1986

French American British (FAB) morphological classification of childhood lymphoblastic leukaemia and its clinical importance.

As part of the Medical Research Council Leukaemia Trial UKALL VIII, 738 unselected children with acute lymphoblastic leukaemia (ALL) had the morphology of their marrow blast cells reviewed by a panel of three haematologists. Ninety four (13%) showed appearances classifiable as type L2 by the French American and British (FAB) cooperative group's criteria, five (0.7%) were typed L3, and the remaining 639 (86%) as L1. Disregarding the patients classified as L3, those with the L2 variant showed an inferior disease free survival to that of the remainder (p less than 0.01), and more of them failed to remit after receiving "standard" remission induction treatment (p less than 0.01). They included an excess of older children (p less than 0.01) with less profound marrow failure at diagnosis, and fewer of them expressed the common ALL antigen (p = 0.05). There was no association between L2 morphology and the diagnostic white cell count, sex, or the presence of a mediastinal mass. These findings confirm earlier reports that FAB L2 ALL is associated with a poor prognosis and that it occurs more commonly in older children. The high remission failure rate is a recent observation and indicates that alternative early treatment may be appropriate for such patients.

Actuarial Analysis↗
PubMed1986

Application of three intragenic DNA polymorphisms for carrier detection in haemophilia B.

In the west of Scotland use of a single intragenic restriction fragment length polymorphism (F9(VIII)/TaqI) allowed definitive genetic counselling for 45% of females at risk of being carriers for haemophilia B. Two further intragenic RFLPs, F9(VIII)/XmnI) and F9(VIII)/DdeI, have been applied to this population and by using all three polymorphisms the carrier status could be determined in 68% of females at risk. Linkage disequilibrium was apparent between these three RFLPs, and in the west of Scotland the single most clinically useful polymorphism was F9(VIII)/TaqI followed by F9(VIII)/DdeI and then F9(VIII)/XmnI. Overall, prenatal diagnosis by DNA analysis could be offered to 31 of 37 (84%) carriers (obligate and detected) in these families.

Cloning, Molecular↗
PubMed1985

Carcinoid syndrome: an unusual cause of diarrhoea.

A 9 year old girl underwent laparotomy because of intermittent diarrhoea, present since infancy. Histology of a mass at the head of pancreas and multiple hepatic nodules suggested an apudoma. Plasma serotonin and urinary excretion of 5 hydroxy indole acetic acid were raised. The child is asymptomatic four years after diagnosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Application of an intragenic genomic probe to genetic counselling for haemophilia B in the west of Scotland.

Total ascertainment revealed 28 families with haemophilia B in the west of Scotland (prevalence 1/26 870 males). In 12 of these families more than one person was affected and 26 living obligate carriers were identified and tested. Of these, 42% were heterozygous for a DNA polymorphism recognised by a factor IX genomic probe. No recombination was observed in 11 phase known and four phase unknown informative meioses. Definitive genetic counselling was possible for 14 of 42 females at risk, 11 could not be traced, in 10 the probe was not informative, and in seven paternal absence prevented interpretation. Linkage disequilibrium was apparent for this restriction fragment length polymorphism and haemophilia B in the west of Scotland.

DNA↗