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Biomedical subjects

P J Hamilton

Publications and source records attributed to P J Hamilton.

At least 19 recordsLinked to original sources
PubMed2003

Dietary folate deficiency with normal red cell folate and circulating blasts.

This report describes a 26 year old woman, of Pakistani origin, who presented five months postpartum with severe megaloblastic anaemia as a result of nutritional folate deficiency. This case was unusual in that a small number of myeloblasts were present in the peripheral blood at presentation, and this circulating population temporarily increased in size when folate replacement was begun. We also highlight the need to recognise the non-linear relation between haematocrit and red blood cell folate concentration when the haematocrit is very low (< 0.15) and emphasise the importance of the clinical history.

Adult↗
PubMed2001

Erythroleukaemia in the north of England: a population based study.

AIMS: To evaluate the incidence and outcome of acute myeloid leukaemia (AML), FAB M6 (erythroleukaemia). METHODS: A demographic study in the Northern Health Region of England between 1983 and 1999. RESULTS: Thirty three cases were diagnosed and registered prospectively. The overall incidence was 0.077 cases/100,000/year. There was a pronounced rise in incidence in patients aged 56 years or more: 6.6 times higher than that in younger patients. Overall survival was poor; median survival was 11 months for those aged less than 56 years, and three months for patients aged 56 years and above (p = 0.045). Acquired karyotypic abnormalities were found in 17 of 27 patients where analysis was attempted. When classified according to the criteria of the Medical Research Council AML trials, karyotype predicted survival, with a median overall survival of 14 months for those with "standard risk" cytogenetic results and two months for "poor risk" results (p = 0.005). CONCLUSION: This study demonstrates a worse survival for patients with erythroleukaemia than that reported in some published trials of selected patients.

Adult↗
PubMed2000

Acquired haemophilia complicating the remission of a patient with high grade non-Hodgkin's lymphoma treated by fludarabine.

We report the development of a high titre antibody to factor VIII in a patient with previous high grade B cell non-Hodgkin's lymphoma treated with fludarabine. Unlike previous reports of factor VIII inhibitors and lymphoproliferative disease this patient's lymphoma was in remission. We speculate that the occurrence of the inhibitor is another manifestation of the increasingly recognized autoimmune side-effects of fludarabine.

Antineoplastic Agents↗
PubMed2000

Management of massive blood loss: a template guideline.

The management of acute massive blood loss is considered and a template guideline is formulated, supported by a review of the key literature and current evidence. It is emphasized that, if avoidable deaths are to be prevented, surgeons, anaesthetists, haematologists and blood-bank staff need to communicate closely in order to achieve the goals of secure haemostasis, restoration of circulating volume, and effective management of blood component replacement.

Blood Component Transfusion↗
PubMed1997

The use of an all oral chemotherapy (idarubicin and etoposide) in the treatment of acute myeloid leukaemia in the elderly: a report of toxicity and efficacy.

Acute myeloid leukaemia (AML) is predominantly a disease of the elderly but such patients are not always appropriate candidates for intensive intravenous (i.v.) based treatment regimens. The development of the anthracycline idarubicin which is highly effective in the treatment of AML and is active when given orally has made it possible to design anti-leukaemic regimens which may be given orally and be particularly useful in those elderly patients with AML considered unsuitable for standard intensive aggressive treatments. We have assessed an oral regimen combining idarubicin 30 mg/m2 and etoposide 80 mg/m2 for 3 consecutive days as initial treatment in 28 elderly patients with AML (median age 69 years, range 56-81) who were not considered suitable for more intensive i.v. chemotherapy schedules. Following informed consent, two patients died before treatment began and one patient withdrew prior to treatment. Twenty-five patients underwent one to four courses of treatment. The schedule was well tolerated with minor nonhaematological toxicity. The first course was given in hospital, eight of 21 subsequent courses of treatment were given entirely as an out-patient. Eleven patients responded to treatment with nine (36%) achieving complete remission (CR). The median survival for all patients was 3 months, but for the nine who achieved a CR it is 9 months with six patients still alive, five in first CR and one in second CR. We conclude that a combination of idarubicin and etoposide given orally as first-line treatment in elderly patients with AML is safe and effective. In some patients this means treatment and follow-up can be given entirely on an out-patient basis.

Acute Disease↗
PubMed1997

Low incidence of myelodysplastic syndrome following transplantation using autologous non-cryopreserved bone marrow.

Between May 1984 and October 1995 we performed 114 autologous stem cell transplants for lymphoma in our centre; 77/114 (68%) were transplanted after primary therapy. The conditioning regimen varied according to diagnosis; 26 patients were conditioned with melphalan and total body irradiation, 66 received melphalan and etoposide and the remainder (50) were conditioned with melphalan alone. The median follow-up is 62 months. Only two new haematological malignancies have occurred, both in patients with Hodgkin's disease. One patient developed Ph+ chronic myeloid leukaemia 18 months post-transplant. In this case, because of the timing of the haematological disorder, we considered the malignancy to be concurrent with or to have preceded the transplant. A second patient developed acute myeloid leukaemia 20 months post-transplant. She had been treated for Hodgkin's disease for 10 years and was transplanted in third complete remission. Cytogenetic analysis in this case showed trisomy 11. We believe this to have been an unequivocal second malignancy. Our finding of a 1.1% incidence of secondary haematological malignancy (95% CI 0.02-4.96) from a census population adds weight to the hypothesis that haematological problems post-transplant reflects prior chemotherapy rather than toxicity from the transplant procedure itself.

Adolescent↗
PubMed1997

Thromboembolic disease associated with ovarian stimulation and assisted conception techniques.

Thromboembolic disease, as a complication of ovarian stimulation and assisted conception techniques, is generally considered to be a rare complication of ovarian hyperstimulation syndrome and, by implication, lower limb in origin. Sporadic cases of unusually sited thromboses, both venous and arterial, have been reported. This paper aims to draw attention to the relatively large number of such thromboses reported in the world literature compared with those cited in previous commentaries, and to emphasize how little is known about their pathogenesis. It is believed that this is an issue which requires to be addressed in order to understand the background pathology to such incidents and if possible to identify women at greatest risk from such potentially debilitating or fatal complications, such that appropriate prophylactic measures can be taken.

Female↗
PubMed1997

Upper limb thrombosis associated with assisted conception treatment.

Three cases of upper limb deep venous thrombosis occurring in association with assisted conception treatment are presented. The accepted argument that lower limb thrombosis occurring in cases of complicated or severe hyperstimulation syndrome represents the likeliest thrombo-embolic disorder in this situation is questioned.

Adult↗
PubMed1995

De novo acute myeloid leukaemia in patients over 55-years-old: a population-based study of incidence, treatment and outcome. Northern Region Haematology Group.

A 4-year prospective study of de novo acute myeloid leukaemia in patients aged 56 years and over was undertaken in the Northern Region of England (population 3.09 million). The study was conducted to assess the incidence and outcome of treatment in all elderly patients diagnosed between January 1, 1988 and December 31, 1991. Two hundred cases de novo AML were confirmed, giving an incidence of 6.05/10(5) per annum (age specific population) (95% Cl, 5.2-6.9). Acute promyelocytic leukaemia was rare. Erythroleukaemia, monocytic leukaemia and AML with trilineage myelodysplasia were more common than in younger patients. Karyotypic abnormalities classically associated with response to therapy were present in only six of 91 patients where cytogenetic data was available. Treatment was at the discretion of the physician in charge: if given, specific treatment was recorded and clinical outcome assessed. Only 84 (42%) of patients received treatment with curative intent. Forty-four of 84 achieved a complete remission, usually of brief duration. A normal karyotype in leukaemic cells was associated with a survival advantage in this group (p < 0.05). Actuarial overall survival at 4 years for the entire group was 2.5%. Even with aggressive treatment, the outcome is poor. The pattern of disease and its lack of response to conventional treatment would support the hypothesis that AML in the elderly may differ biologically from that observed in younger patients. Karyotyping appears to predict those patients likely to benefit from intensive therapy and decisions about management in otherwise fit patients should, if possible, be delayed until a result is obtained. Every effort should be made to give such patients optimal treatment. However, most patients are unsuitable for aggressive treatment and, since long-term survival is rare, cure should not be offered as an inducement to accept such treatment and improving quality of life outside hospital should be the aim of treatment in this group.

Acute Disease↗
PubMed1995

Evaluation of the impact of allogenic transplant in first remission on an unselected population of patients with acute myeloid leukaemia aged 15-55 years. The Northern Regional Haematology Group.

The aim of this study was to collect prospectively unselected, population-based data on young adults with acute myeloid leukaemia (AML) over a 9-year period and to evaluate the impact on survival of the introduction of allogeneic transplantation performed in first remission. The population within the Northern Region of England is 3.09 million. During the study period a total of 149 de novo patients between 15 and 55 years old presented. The incidence of AML was 0.79 per 10(5) (age-specific population) in the 15-24-year-old group, 0.85 per 10(5) in the group 25-39 years old and 1.35 per 10(5) in the 40-55-year-old group. Remission induction success varied with age (74% for patients < 40 years and 58% for patients 40-55 years). In the 15-40 year old group 28 patients had an HLA-matched donor, 22 patients had a transplant (one syngeneic) and 24 patients in the 15-40-year-old group in remission at 6 months did not have a transplant. The allogeneic group < 40 years old had an event-free survival (EFS) at 4 years of 62%, whereas patients of the same age who received chemotherapy alone had an EFS at 4 years of 24%. A small heterogeneous group of 14 patients who had intensification with autotransplant are not included in this analysis. The population study approach demonstrates the difficulties of introducing uniform treatment strategy in this disease group. The study confirms the view that allogeneic transplant in first remission in the 15-40-year-old group is the treatment of choice. Unfortunately the overall impact of transplant on the population is not great since only 22 of 149 patients (14%) were able to receive an allograft in first remission.

Adolescent↗
PubMed1995

Role of target organ infection with cytomegalovirus in the pathogenesis of graft-versus-host disease.

Skin and rectal biopsy tissue from 34 allogeneic and 23 autologous BMT recipients was prospectively analysed for CMV using immunohistochemistry and PCR to investigate the hypothesis that target organ infection with CMV initiates and/or exacerbates GVHD. Biopsies were obtained prior to and at 3, 8 and 26 weeks after BMT and whenever GVHD was suspected. Surveillance specimens of peripheral blood leucocytes (PBL), urine and throat swabs were obtained every 2 weeks until 12 weeks after BMT, and whenever CMV was suspected. Cryostat sections were analysed immunohistochemically for CMV antigens and PBL and biopsies for CMV DNA by PCR. Of the 31 patients who engrafted, 28 (90%) developed GVHD clinically, confirmed histologically in 56 biopsies. GVHD proved clinically severe in 14 patients, 4 of whom had treatment-resistant GVHD. CMV was detected in PBL more frequently in patients with severe GVHD than in those with mild/moderate GVHD (29% vs. 7%). However, in all but one patient the onset of GVHD preceded detection of CMV. In biopsy specimens, CMV was detected in only 2 patients, 1 of whom had an exacerbation of GVHD temporally associated with CMV. Thus, despite a high incidence of GVHD in this series, with 56 episodes of GVHD in 28 patients, only 1 patient had CMV in biopsy tissue temporally associated with GVHD. This suggests that biopsy infection with CMV is not a major factor in initiating or exacerbating GVHD in this cohort. This study thus does not support a role for target organ infection with CMV in the pathogenesis of GVHD.

Adolescent↗
PubMed1994

Assessing iron status in children with chronic renal failure on erythropoietin: which measurements should we use?

Iron deficiency severely limits the efficacy of recombinant human erythropoietin (EPO). In order to determine how best to identify and monitor children at risk of developing iron deficiency, we serially measured several parameters of iron status in nine children before and during a 24-week period of EPO therapy. Serum ferritin was the best predictor of development of iron deficiency, five of the nine children developed iron deficiency, characterised by a poor haemoglobin response or evidence of microcytosis and hypochromia; all had a serum ferritin of 60 micrograms/l or less at the start of EPO. Haemoglobin response was also related to change in mean red cell volume (MCV); a falling MCV, irrespective of absolute value, accompanying a poor response to EPO. Iron treatment in five children resulted in significant improvements in haemoglobin and iron status parameters. Although MCV remained low, there was a marked increase in red cell volume distribution width after iron, which may be of value in monitoring the response to iron therapy. We suggest that children with a serum ferritin of 60 micrograms/l or less and those who develop a falling MCV during EPO treatment should receive high-dose oral iron supplementation before and during treatment with EPO.

Administration, Oral↗
PubMed1994

The relationship between bcl-2 expression and response to chemotherapy in acute leukaemia.

Immunocytochemistry was used to assess bcl-2 expression in blasts obtained from the bone marrow of 28 patients with acute lymphoblastic leukaemia (ALL) (16 children and six adults at presentation and three children and three adults on relapse) and 20 with acute myeloid leukaemia (AML) (19 adults and one child, 13 with de novo AML, 11 at presentation and two on relapse, and seven secondary to myelodysplasia or chronic myeloid leukaemia). Slides were examined both for the percentage of positive cells and for the intensity of staining using a five-point scale. There was a statistically significant increase in both the percentage of positive cells seen (P < 0.002) and the intensity of staining (P < 0.01) between samples obtained at relapse and those at presentation in ALL. There was a significantly greater intensity of staining in cells from patients with ALL (P < 0.05) and AML (P < 0.05) who failed to achieve remission after chemotherapy than in those who responded. The intensity of staining in cases of secondary AML was lower than that in de novo disease (P < 0.01). These results suggest that expression of bcl-2 may be an important prognostic feature in both de novo AML and in ALL, but not in secondary AML.

Adolescent↗