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Biomedical subjects

I M Hann

Publications and source records attributed to I M Hann.

At least 55 records · Page 3Linked to original sources
PubMed1995

Pearson's marrow/pancreas syndrome: haematological features associated with deletion and duplication of mitochondrial DNA.

Pearson's marrow/pancreas syndrome (PS) is a rare, often fatal, disorder of infancy that is characterized by impaired bone marrow, exocrine pancreatic, hepatic and renal function. Large-scale rearrangements of mitochondrial DNA (mtDNA) are present in blood. We report a patient with PS who has predominantly impaired haemopoiesis manifesting as sideroblastic anaemia, vacuolization of bone marrow precursors, and neutropenia. 77% of bone marrow mtDNA was rearranged (64% deleted an 13% duplicated). We suggest that rearrangements of mtDNA should be sought in all infants presenting with sideroblastic anaemia.

Anemia, Sideroblastic↗
PubMed1995

Use of central venous catheters in children with severe congenital coagulopathy.

From two U.K. centres 23 children with severe congenital coagulopathy had a total of 27 port-a-cath devices inserted to facilitate factor VIII or IX prophylaxis (eight patients), domiciliary therapy (seven patients), immunotolerance (four patients), or a combination thereof (four patients). Six children had a factor VIII inhibitor at the time of insertion. The mean age at operation was 30 months, with a range of 9-76 months. The cumulative length of follow-up is 639 months with a mean of 27.8 months and a range of 5-79 months. Haemostasis was achieved peri- and post-operatively with high-purity concentrate in the majority of patients without an inhibitor. All those with an inhibitor had porcine factor VIII, except one who had recombinant factor VIIa. The post-operative complication rate was 27% (6/23): three had a port-site haematoma (one required removal and replacement), two had post-operative infection, and one had swelling caused by extravasation. To date there have been 13 documented infections in 10/23 patients (five with inhibitor): a rate of 0.24 per follow-up year or 0.67 per 1000 patient-days. Six were caused by Gram-positive and seven by Gram-negative organisms. Six infections could not be eradicated by antibiotics and the port-a-cath system had to be removed; in three it was replaced by a second port-a-cath. Although there are risks involved in the use of port-a-caths in this population, both clinicians and parents involved in the care of these children believe that the benefits are considerable and the potential hazards are acceptable.

Blood Coagulation Disorders↗
PubMed1995

Visceral leishmaniasis: rapid response to AmBisome treatment.

There appears to be an increase in imported cases of visceral leishmaniasis in Northern Europe; many are children infected on holiday in the Mediterranean. Making the diagnosis in young children can be difficult especially when an adequate travel history is not obtained at presentation. Two infants with visceral leishmaniasis are presented who were initially felt to have alternative diagnoses and who subsequently responded dramatically to a short course of liposomal amphotericin B (AmBisome).

Amphotericin B↗
PubMed1995

Changes in cytomorphology of childhood lymphoblastic leukaemia at the time of disease relapse. Childhood Leukaemia Working Party of the United Kingdom Medical Research Council.

AIMS: Children in a United Kingdom national trial for relapsed non-B lymphoblastic leukaemia (ALL) had their diagnostic and relapse marrow cytomorphology compared to see what changes occur during the evolution of the disease. METHODS: Each relapse slide was assessed blindly for French American British (FAB) type and other morphological features by a panel of three independent microscopists without reference to each other or any diagnostic material. Diagnostic slides had been assessed by the same panel on an earlier occasion. RESULTS: A total of 134 consecutive children was studied. Six (5%) were classified as FAB type L2 at diagnosis, compared with 18 (13%) at relapse (a difference of 9%). Twenty two (16%) changed their FAB type, 17 (13%) from L1 to L2 and five (4%) from L2 to L1. The FAB score fell at relapse in 34 children and rose in 14, a difference of 14%. Cell size was the commonest feature to change (increasing in 22 and diminishing in nine) followed by prominent nucleoli (appearing in 21 and disappearing in six). Forty four (33%) children had vacuolated blasts at diagnosis, compared with 48 (36%) at relapse. Twenty five changed their vacuole score substantially, 14 gaining > 10% and 11 falling < 10%. CONCLUSIONS: These findings reflect the variability of lymphoblast cytomorphology, but also show a trend for cells to have more prominent nucleoli and greater size at relapse. Factors controlling these features of the FAB type are unknown, but they may simply be related to the growth fraction of a particular disease and not to any lineage specific biological feature.

Adolescent↗
PubMed1994

Late effects of intensive treatment for acute myeloid leukemia and myelodysplasia in childhood.

PURPOSE: To perform a comprehensive assessment of the late effects of short-term intensive chemotherapy for childhood acute myeloid leukemia (AML) and myelodysplasia, and compare the sequelae of intensive chemotherapy alone with those of total-body irradiation (TBI). PATIENTS AND METHODS: Of 33 survivors studied, 26 (group A) received intensive chemotherapy including anthracyclines, one also received busulfan, cyclophosphamide (Bu/Cy), and bone marrow transplantation (BMT). Seven patients (group B) received chemotherapy, TBI, and BMT. Hearing, sight, growth, and endocrine, renal, and cardiac function were assessed. RESULTS: The mean height standard deviation score of 25 nontransplanted group A patients was +0.67 at diagnosis, -0.11 following treatment (P = .016), and +0.34 7 years later (P > .05), indicating no long-term growth impairment. The patients had normal gonadal function and the girls had normal uterine size and ovarian volume. The Bu/Cy patient had primary ovarian failure. Four group B children required growth hormone and four sex steroids for growth or gonadal failure. The girls had reduced uterine size and ovarian volume. Three had thyroid dysfunction and six had cataracts. Abnormalities of renal function were found in both groups and hearing loss in group A only. The mean cardiac shortening fraction was significantly reduced at 29.2% in group A and 28.6% in group B compared with 36% in normal subjects. Two group A patients have developed cardiac failure. CONCLUSION: Chemotherapy and TBI before BMT for AML has resulted in growth failure, gonadal and thyroid damage, and cataracts in most children, whereas chemotherapy alone caused cardiac, renal, and hearing abnormalities only.

Acute Disease↗
PubMed1994

Early deaths in children undergoing marrow ablative therapy and bone marrow transplantation.

We have reviewed the causes and risk factors for early death in a group of 295 children who underwent any form of first bone marrow transplantation (BMT) between 1978 and 1992. The commonest indications for transplantation were acute lymphoblastic leukaemia 80 (27.1%), neuroblastoma 69 (23.3%), immune deficiency 57 (19.3%) and myeloid leukaemias/myelodysplasia 50 (16.9%). There were 120 (40.6%) allogeneic BMTs, 118 (40%) autologous BMTs, while 51 (17.2%) children usually with severe combine immune deficiency received BMT from a non-HLA-identical parent, sibling or other relative (FBMT). Two were from identical twins and four from matched unrelated donors (MUD). Thirty-three children (11.2%) died in the first 100 days; the main causes of death being infection (n = 5), relapse (n = 7), graft failure (n = 4), GVHD (n = 7) and organ failure with or without infection (n = 6). There was no significant change in the incidence of early deaths in the three successive 5 year periods (1978-82, 1983-87, 1988-92) although there was some shift in the causes. Infections were the commonest cause during the first 5 year period, relapses followed by GVHD in the second period and single organ failure followed by GVHD and infections in the third period. The main causes of early death were relapse after high-dose chemo/radiotherapy and autologous BMT (7 of 9 deaths) and GVHD and infection after allogeneic BMT (9 of 13 deaths). In the group of 51 children undergoing FBMT there were five deaths from infection, three from graft failure, one from organ failure and one from GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Aplastic↗
PubMed1992

Cytomorphology of childhood lymphoblastic leukaemia: a prospective study of 2000 patients. United Kingdom Medical Research Council's Working Party on Childhood Leukaemia.

Blast cell morphology of children with lymphoblastic leukaemia (ALL) entering two national multicentre trials was prospectively reviewed by three haematologists to define the clinical importance of (a) French-American-British (FAB) classification, (b) the presence of cytoplasmic vacuoles, and (c) the presence of 'hand-mirror' cells. Of 2135 evaluable children, 1907 (89%) had FAB L1 morphology and 228 (11%) L2. (L3 patients were not eligible for the trials in question). L2 patients more frequently had residual disease 14 d after starting treatment and had a significantly inferior disease-free survival, but not if the analysis was stratified for age, sex and diagnostic white cell count (WBC). 627 (29%) had blast cells with cytoplasmic vacuoles, and showed a significant survival advantage over the remainder. Vacuoles were positively associated with a low WBC, age range 1-6 years and blast cell positivity for CD10, but their benign influence was apparent even when these variables were taken into account. 'Hand-mirror' (HM) cells were only studied in UKALL X, and were noted in 316/1402 (23%) children. There appeared to be an inverse correlation between HM cells and cytoplasmic vacuoles and a weak association with T-cell immunophenotype, but no prognostic significance was evident. FAB classification appears to be of less prognostic importance than has previously been supposed, though L2 disease is more resistant to current remission induction regimens. Hand-mirror cells may be more common in T-ALL, but are seen in all types and are not related to prognosis. Cytoplasmic vacuoles are predictive of a good response to current therapeutic schedules even allowing for other prognostic variables, and are the single most important morphological feature relating to prognosis in childhood ALL.

Adolescent↗
PubMed1992

Intensive chemotherapy with or without additional bone marrow transplantation in paediatric AML: progress report on the MRC AML 10 trial. Medical Research Council Working Party on Childhood Leukaemia.

The Medical Research Council's AML 10 Children Trial commenced in 1988. It is a multicentre collaborative study based on 4 courses of intensive chemotherapy with additional allogeneic bone marrow transplantation for children with a matched sibling donor. The remaining children are randomised either to an autologous transplant using unpurged marrow or stopping therapy. To date 156 eligible patients have been entered with a CR rate of 91%. 56% of children are still alive 2 years after trial entry and 57% are in CR 3 years after achieving CR. The treatment regimen is intensive but mortality and morbidity are acceptable. The study will need to accrue patients for a further 2 to 3 years in the hope of defining the role of allogeneic and autologous marrow transplantation.

Acute Disease↗
PubMed1991

Acquired aplastic anaemia: still a serious disease.

Over 15 years, 42 children aged 2-14 years were diagnosed as having acquired aplastic anaemia. Adequate clinical details were available for 38 children who were categorised as very severe (n = 13), severe (n = 16), or nonsevere (n = 9) by the modified Camitta criteria. Treatment varied over the study period. Seven children received a bone marrow allograft from a full match family donor and three a matched unrelated donor transplant after failed treatment with antilymphocyte globulin. The remainder were treated with antilymphocyte globulin (n = 11), antilymphocyte globulin and oxymetholone (n = 4), oxymetholone with or without prednisolone (n = 12), or supportive treatment alone (n = 1). With a minimum follow up of one year since treatment, the five year survival was 70% for bone marrow transplantation with a family donor, 30% for antilymphocyte globulin, and 25% for oxymetholone. All three children with a matched unrelated donor transplant died. The prognosis of acquired aplastic anaemia remains poor for most children and new approaches to treatment are urgently required.

Adolescent↗
PubMed1990

Psychological disturbance in children with haemophilia.

OBJECTIVE: To assess the need for formal psychotherapeutic intervention in children attending a children's haemophilia clinic after some of them had been diagnosed as positive for HIV. DESIGN: Comparison of haemophiliac children with matched control groups of diabetic and healthy children. SETTING: The West of Scotland Children's Haemophilia Centre, Glasgow. PATIENTS: 43 Children aged 3 to 16 years with mild, moderate, and severe clotting disorders were matched with control groups of 46 diabetic children and 42 physically healthy children. INTERVENTIONS: Parents of children aged 3-5 years were interviewed with the behaviour screening questionnaire. Children aged 6 to 16 were assessed by parental and teacher report using standardised questionnaires and self report using a computerised depression inventory. All were scored numerically according to the presence of symptoms of emotional and behavioural problems. MAIN OUTCOME MEASURES: The groups were compared for mean scores on each rating device and for number of children achieving scores within the pathological range. RESULTS: In the 6-16 age group five haemophiliac children, five diabetic children, and three healthy children scored in the pathological range on the parent questionnaire, as did two, three, and five respectively on the teacher questionnaire and four, four, and eight on the depression inventory. There was no significant difference across the three groups. Analysis of mean scores similarly showed no significant difference across groups. In contrast, the single measure used for younger children showed an increase in behavioural difficulties among the diabetic children. CONCLUSION: Haemophiliac children attending the West of Scotland Centre were no more disturbed than their diabetic or healthy peers despite the identification of HIV infection within the clinic and the widespread adverse publicity associated with AIDS and HIV infection.

Adolescent↗
PubMed1990

Tumor spheroid model for the biologically targeted radiotherapy of neuroblastoma micrometastases.

Neuroblastoma is a pediatric malignancy with a poor prognosis at least partly attributable to an early pattern of dissemination. New approaches to treatment of micrometastases include targeted radiotherapy using radiolabeled antibodies or molecules which are taken up preferentially by tumor cells. Multicellular tumor spheroids (MTS) resemble micrometastases during the avascular phase of their development. A human neuroblastoma cell line (NBl-G) was grown as MTS and incubated briefly with a radiolabeled monoclonal antibody (131I-UJ13A) directed against neuroectodermal antigens. Spheroid response was evaluated in terms of regrowth delay or proportion sterilized. A dose-response relationship was demonstrated in terms of 131I activity or duration of incubation. Control experiments using unlabeled UJ13A, radiolabeled nonspecific antibody (T2.10), radiolabeled human serum albumin, and radiolabeled sodium iodide showed these to be relatively ineffective compared to 131I-UJ13A. The cell line NBl-G grown as MTS has also been found to preferentially accumulate the radiolabeled catecholamine precursor molecule m-[131I]iodobenzylguanidine compared to cell lines derived from other tumor types. NBl-G cells grown as MTS provide a promising laboratory model for targeted radiotherapy of neuroblastoma micrometastases using radiolabeled antibodies or m-iodobenzylguanidine.

Antibodies, Monoclonal↗
PubMed1990

'MACHO' chemotherapy for stage IV B cell lymphoma and B cell acute lymphoblastic leukaemia of childhood. United Kingdom Children's Cancer Study Group (UKCCSG).

An intensive 6-month schedule of drugs was devised with both systemic and central nervous system activity, known by the acronym 'MACHO', to treat 24 newly and consecutively diagnosed children, 13 with stage IV B-cell non-Hodgkin's lymphoma (B-NHL) and 11 with B-cell acute lymphoblastic leukaemia (B-ALL). There were three deaths from complications of chemotherapy (two infective, one biochemical). Five children with central nervous system disease at diagnosis (CNS+) received planned additional megatherapy/bone marrow transplants. Event-free survival (EFS) at 1 year for the 11 cases of B-ALL is 64% (95% confidence intervals [CI] 31-89%) and of 13 stage IV B-NHL cases is 50% (95% CI 19-75%). Patients with bulky abdominal disease had a 32% EFS at 1 year (CI 13-68%) compared with 76% (CI 39-94%) for those without bulky abdominal disease. Overall EFS for eight CNS+ patients is 73% at 1 year (95% CI 34-97%) compared with 48% (95% 24-74%) for those without CNS disease (CNS-). However, only two of the CNS+ cases had bulky abdominal disease (patients 10 and 12) and the difference is not significant (P less than 0.5). A score of 1 was given for each of the following potential prognostic features: bulky abdominal disease, pleural effusion and severe renal dysfunction within 48 h of presentation. Patients who scored 0 or 1 fared significantly better than those who scored 2 or 3 (EFS at 1 year 78% [CI 49-95%] versus 24% [6-65%], P less than 0.04). Two patients with a score of 2 survived past 6 months and another is currently well, but has not regenerated his marrow following autologous transplantation. This protocol is relatively effective for patients who have B-ALL, but those patients who have bulky abdominal disease, often associated with severe renal dysfunction, and those with CNS disease, do not fare so well and require new approaches to therapy.

Adolescent↗