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Biomedical subjects

Lucille Wood

Publications and source records attributed to Lucille Wood.

At least 19 recordsLinked to original sources
PubMed2005

The effect of peptide stimulation on haematopoietic stem cell mobilisation including engraftment characteristics and a note on donor side effects.

Aplasia or irreversible bone marrow failure and a variety of haematologic malignancies, as well as an increasing number of solid tumours, currently include various forms of marrow or equivalent transplantation in routine management. In both allogeneic and autologous procedures stable recipient immunohaematopoietic reconstitution depends upon infusing the requisite population harvested at a precise time following commencement of a stimulatory peptide. In a first step this prospective study documented the safety of apheresis, defined side effects and enumerated mononuclear, CD34+ and CD3+ cells obtained. In the second stage delivery of the graft, characterised in this way and with the additional measurement of in vitro growth in clonogenic assay, to the suitably conditioned patient was correlated with recovery of neutrophil and platelet numbers appearing in the circulation. In a third and ongoing analysis the influence of passenger T-lymphocytes is being evaluated for impact on infection and a potential anti-tumour effect. The conclusion is that this technology is reliable, has a high degree of patient acceptability without untoward complications, and that local results correspond to international experience thereby providing an important and relevant measure of quality control.

Antigens, CD34↗
PubMed2005

Estimation and predictive use of the corrected count increment--a proposed clinical guideline.

BACKGROUND AND OBJECTIVE: Platelets are frequently given inappropriately. The accepted indication is symptomatic thrombocytopaenia due to bone marrow failure. In contrast replacement therapy is contraindicated in immune mediated peripheral sequestration because it is almost always ineffective and also aggravates the already rapid rate of the clearance due to superimposed isoimmunisation. Furthermore circulating levels, rather than the clinical situation, customarily trigger the request and would typically be at 20 x 10(9)/l. Usage is under evaluated and, accordingly, current practice has been scrutinised and a guideline proposed that is applicable to user and vendor alike. DESIGN AND METHODOLOGY: Prospectively a consecutive series of eligible cases were selected and, with informed consent, all relevant information recorded. Specific observations were haematologic status, quality of the product and the impact of previous exposure to blood fractions on outcome. Additionally, factors that influence response were documented and included disseminated intravascular coagulation, splenomegaly and concurrent use of intravenous Amphotericin B. The absolute numbers infused, the increase in peripheral value recorded and this ratio which is designated as corrected count index generated in each instance. RESULTS: The CCI was computed for each of the 85 megaunits given to 29 individuals and subsequently estimated for the entire sample population using regression analysis. Each of the variables was used to test the hypothesis that such a figure might differ depending on patient sub-population. This approach was accurate in 60% of the time and predicates a more rational use of donor characteristics. The cardinal measurement is that supplied by the transfusion service which can be used as a basis for clinically important predictors of anticipated benefit. CONCLUSION: This data, in keeping with international practice, leads to the recommendation that commercial and other services routinely measure and specify absolute numbers. The clinicians, reciprocally, should always confirm this figure and then match anticipated to observed outcome. Failure to carry out these simple procedures lead to gross over utilisation of this expensive intervention, risks unnecessary sensitisation and furthers persistence with sub-optimum administration.

Blood Component Removal↗
PubMed2005

Clonogenic growth patterns correlate with chemotherapy response in acute myeloid leukaemia.

Cytosine arabinoside and anthracycline-containing regimens induce remission in upwards of 60% of previously untreated patients with adult acute myeloid leukaemia (AML). Despite this, in addition to primary drug resistance, the majority of these patients relapse. Reliable methods for uniformly recognising these two subgroups at presentation do not exist and therefore a further attempt has been made to relate in vitro toxicity, using a clonogenic assay, to clinical outcome. In 10 normal controls and 12 chemotherapy naïve cases, mononuclear cells harvested by density gradient separation were re-suspended at a concentration of 2 x 10(5)/ml and quadruplicates of 250 microl per well cultured in methycellulose containing foetal calf serum and phytohaemagglutinin stimulated leucocyte conditioned medium. Cell kill was determined for cytosine arabinoside, daunorubicin and etoposide either singly or in combination using both a pulsed and continuous exposure. Aggregates were scored after seven days and three distinct patterns recognised. The patients all received the same drugs in a standard protocol and achievement of complete remission correlated with growth pattern. The survival of normal marrow colony-forming cells or GM-CFUc and the leukemic equivalent designated L-CFUc were assessed and a sensitivity index (SI) determined as a ratio of these two values in which more reproducible results were found when the drug was continuously present. It is concluded that the microculture technique is feasible and clearly demonstrates chemotherapy effect but no correlation was demonstrated with clinical outcome. This is a negative pilot study and, as a means of recognising drug sensitivity or resistance, should be discarded in favour of currently available molecular techniques.

Adolescent↗
PubMed2005

Splenectomy in haematology--a 5-year single centre experience.

OBJECTIVE: To define indications and outcome in haematologic cases undergoing splenectomy. STUDY DESIGN: A retrospective review of clinical records from consecutive patients having open or laparoscopic removal of the spleen in an academic centre in the private sector. Endpoints were survival, operating time, spleen size, histopathology, requirements for blood or related products complications and average costs. RESULTS: In the total group (n = 69) there were two deaths. Referrals were for immune thrombocytopaenia (41%), acquired haemolytic anaemia (10%), myeloproliferative syndrome (9%), acute or chronic leukaemia (19%), lymphoma (13%) and a miscellaneous group (8%), comprising cholelithiasis, aplasia or as a diagnostic procedure for otherwise unexplained splenomegaly. An open midline approach was predicated by spleens greater than twice normal size and a history of any bleeding disorder. Here the mean operating time was 83 min (range 40-295) whereas for laparoscopy this was 251 min (range 181-272). SUMMARY: Careful stratification between the two options facilitated optimum haemostasis and consequently reduced requirement for packed red cells and platelets. Neither underlying pathology nor the choice of treatment influenced morbidity or mortality. Overall local experience is consistent with published international standards of surgical practice. Outcome is directly proportional to the number of each procedure carried out by a single team, observance of consistent protocols for preoperative evaluation and standardized proactive management through the recovery period.

Adolescent↗
PubMed2005

Silent angiodysplasia and occult haemobilia as rare but treatable causes of refractory iron deficiency--two case reports.

Once menorrhagia has been excluded in females then, in both sexes, the gastrointestinal tract remains the commonest site for haemorrhage. This may be of surprisingly large volume but intermittent and therefore not universally demonstrated on stool testing. However, if loss is persistent it may nevertheless culminate in absolute iron deficiency and thus, even when occult blood is not present on repeated examinations, quantitation using chromium labelled red cells becomes invaluable. In this situation, endoscopy or contrast radiology of the small and large bowel may fail to reveal any lesion even when these procedures are repeated or used in combination. Modifications by direct inspection or camera study may be helpful in improving diagnostic accuracy. It is nevertheless practical, as illustrated by these two cases, to more widely recognise the value of radionuclide scanning methods. In one this was due to unsuspected haemobilia and the second to major duodenal vascular malformation although it could be reasonably argued that initial recourse to angiography might have demonstrated this. The principle is that when precisely defined anatomically surgery can be elective and limited as a result of careful proactive planning and operations likely to have a high initial rate of success. The role of nuclear medicine in the investigative algorithm of such patient is re-emphasised. Thus, in any individual with unexplained but proven absolute iron deficiency failure to reveal the cause by first screening with gastroscopy and colonoscopy or barium studies including the small bowel should not automatically be repeated. Rather, the blood loss needs to be documented and, if possible, subsequent evaluation moved to advancement or push enteroscopy, capsule endoscopy or the more invasive angiography only once quantity a pattern of bleeding are defined by radioisoptic imaging.

Adult↗
PubMed2004

Macronutrients.

Explore the source record for details and available documents.

Deficiency Diseases↗
PubMed2003

Eradication of invasive mucormycosis--effectiveness of the Echinocandin FK463.

BACKGROUND: Invasive rhinocerebral mucormycosis is a rare and often fatal opportunistic fungal infection. It is encountered in immunocompromised hosts exemplified by those with diabetes, human immunodeficiency viruses and particularly haematologic malignancies typically after high-dose chemotherapy and stem cell transplantation. In contrast to the more usual outcome with rapid progression and death. We now describe a successful eradication attributable to the use of a newly available antifungal agent. SETTING: Haematology department and bone marrow transplantation unit. MATERIAL AND METHOD: Two patients are contrasted. The first with acute leukaemia developed rapidly progressive facial swelling with mucormycosis proven on biopsy. Treatment over 2 months with maximally tolerated doses of amphotericin failed to halt intracranial extension and death resulted. The second, presented with acute lymphoblastic leukaemia in August 1997, underwent successful autologous bone marrow transplantation in February 1998. Relapse followed in March 1999 and after reinduction and consolidation receive a matched unrelated volunteer allograft in September 1999. A second recurrence was documented in April 2000 and in spite of achieving remission he developed a fever that was managed empirically with intravenous amphotericin and, on discharge, oral itraconazole. Left-sided facial swelling expanded rapidly and biopsy showed extensive invasion of the maxillary sinus with mucormycosis. FK463 was added on 5 June 2000 with gradual reduction in facial pain and within 1 month all clinical signs and resolved. Serial biopsies that included histopathologic investigation and microbiologic cultures confirmed eradication of the invasive mucor. In view of the potential danger of recrudescence this treatment regimen was continued through further chemotherapy and, once again disease-free, a second matched unrelated volunteer allograft took place in August 2000. Full reassessment at the time failed to demonstration any residual fungus. Engraftment was confirmed but neutropenic sepsis resulted in severe inflammatory response syndrome with progression to multiple organ dysfunction to which he succumbed without any evidence of leukaemic or systemic mycosis. CONCLUSION: Echinocandin FK463 is of documented value in managing invasive candidiasis and aspergillosis. This is believed to be the first case of successful outcome with one of the angiotrophic zygomycetes.

Acute Disease↗
PubMed2002

Myelodysplasia and the acute myeloid leukaemias.

The myelodysplastic syndromes are increasingly recognised clinical entities reflecting a stem cell defect that gives rise to ineffective clonal haematopoiesis. The spectrum extends from relatively indolent refractory anaemia through varying combinations of leucopoenia and thrombocytopenia to acute leukaemia. Diagnosis rests on marrow hypercellularity with dysplastic morphology, apoptosis and, often distinctive cytogenetic defects. Stratification to risk-related protocols range from occasional blood transfusions or erythropoietin through innovative options including thalidomide or amifostine to haematopoietic stem cell transplantation in selected individuals. Acute myeloid leukaemia, conceptually segregated from preleukaemia, is treated differently although accumulating cellular and molecular data favour a more integrated approach. Morphology and immunophenotyping are complemented by molecular genetics. On this basis chemotherapy alone is sufficient in defined sub-groups whereas others benefit by autologous or allogeneic grafting. Attention to demonstrating minimal residual disease is the basis for more specific intervention exemplified by monoclonal antibodies or maturation-inducing agents as with retinoic acid in acute progranulocytic leukaemia

Acute Disease↗
PubMed2002

Chronic lymphocytic leukaemia--the haematologic basis for diagnosis and treatment.

Clinically diagnosis may be incidental when absolute lymphocytosis is uncovered at routine medical examination. More usually there is a recurrent sinopulmonary infection reflecting a varying degree of humoral and cellular immune deficiency. Autoimmune phenomena may result in haemolytic anaemia or thrombocytopenia. Expanding tumour bulk underlies the lymphadenopathy which may be prominent. Diagnosis is confirmed on morphology of the smear where atypical variants need to be distinguished from other indolent lymphoproliferative disorders. Immunophenotyping is indispensable in classification. Prognosis is predicated by cytogenetics and markers of tumour biology that include beta-2 microglobulin and peripheral blood lymphocyte doubling time. Management is dictated by symptoms and signs of progression superimposed upon performance status that includes age. Disease that is asymptomatic and truly indolent, particularly in the elderly, qualifies for a careful watch-and-wait policy. In other circumstances stratification to therapy requires entry into peer-reviewed protocols if optimal outcome is to be achieved. Established regimens, of demonstrably equal efficacy, are pulsed single-agents exemplified by chlorambucil or combinations of cyclophosphamide with vincristine and prednisone. The purine analogues, particularly when administered with an alkylating agent and mitoxantrone, are emerging as superior options. In selected patients any properly accredited program will make provision for escalation in chemotherapy requiring haematopoietic stem cell transplantation on the one hand or use of serotherapy with CD52 antibodies on the other. Less commonly, but in a defined subgroup, immunoglobulins directed against membrane CD20 may be effective. Perspective for the generalist is anchored in recognising that the previous cavalier approach to drug medication, with or without radiotherapy, is unwise whereas integrated management is now the international standard of practice. The previous anachronism of dabbling by occasional therapists is to be deprecated since this will generally deny patients access to proper diagnosis and risk-adjusted multi-disciplinary treatment.

Antineoplastic Agents↗