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J D Cavenagh

Publications and source records attributed to J D Cavenagh.

35 records · Page 2Linked to original sources

A CD4+ proliferation of large granular lymphocytes expresses the protease activated receptor-1.

The platelet-type thrombin receptor was the first member to be identified in a family of protease activated receptors (PARs) and has been designated PAR-1. We recently reported that the large granular lymphocytes (LGLs) in patients with proliferations of CD8+ cells co-expressed PAR-1 and the expression of PAR-1 correlated with the expression of CD57. Here we show, by three-colour immunofluorescence, that the LGLs from a patient with a rare CD4+ CD57+ monoclonal expansion also expressed PAR-1. Northern blot analysis confirmed the presence of high levels of mRNA for PAR-1 in these LGLs.

Aged↗

Adhesion molecules in clinical medicine.

Cellular adhesion molecules (CAMs) are critical components in the processes of embryogenesis, tissue repair and organization, lymphocyte function, lymphocyte homing and tumor metastasis, as well as being central to the interactions between hemopoietic progenitors and bone marrow microenvironment, and between leukocytes and platelets with vascular endothelium. Expression of CAMs regulates normal hemopoiesis and migration and function of mature hemopoietic cells. CAMs are an important part of the inflammatory response and may regulate cytokine synthesis. In addition, CAM expression may be critical for tumorigenesis. Monoclonal antibodies to CAMs have been developed for clinical use; initial results suggest that these agents have great potential in the prevention and treatment of inflammation, thrombosis, reperfusion injury, and graft rejection.

Antibodies, Monoclonal↗

Early evaluation of liposomal daunorubicin (DaunoXome, Nexstar) in the treatment of relapsed and refractory lymphoma.

We have treated 19 patients with relapsed or refractory lymphoma with liposomally encapsulated daunorubicin (DaunoXome) at two dose schedules; 40 mg/m2 repeated every 14 days and 120 mg/m2 repeated every 21 days. Non-haematological toxicity was mild, in particular, no patient treated with the higher dose schedule showed clinical deterioration in cardiac function. At the lower dose (10 patients) no objective responses were seen but at the higher dose (9 patients) one complete response and two partial responses were achieved. Liposomal daunorubicin at 120 mg/m2 appears to have some activity against refractory lymphoma and we suggest that further studies with this agent are required.

Adult↗

Thymic function in adults: evidence derived from immune recovery patterns following myeloablative chemotherapy and stem cell infusion.

We studied 45 patients aged 14-66 years who had undergone stem cell transplantation for a variety of malignant conditions at least 12 months previously. Compared to normal controls, they had significantly reduced absolute numbers of CD4+, CD4+ CD45RA+ and CD4+ CD45RO+ T cells and a reduced CD4+ CD45RA+:CD4+ CD45RO+ ratio. In all subsets T-cell numbers were significantly greater 24 months, compared to 12-24 months, after transplantation and there was a nonsignificant trend towards lower T-cell numbers with increasing age. We conclude that the thymus, or putative thymic-equivalent tissue, remains functional in older adults.

Adolescent↗

Haematological validation of a computer-based bone marrow reporting system.

AIMS: To prove the safety and effectiveness of "Professor Belmonte", a knowledge-based system for bone marrow reporting, a formal evaluation of the reports generated by the system was performed. METHODS: Three haematologists (a consultant, a senior registrar, and a junior registrar), none of whom were involved in the development of the software, compared the unedited reports generated by Professor Belmonte with the original bone marrow reports in 785 unselected cases. Each haematologist independently graded the quality of Belmonte's reports using one of four categories: (a) better than the original report (more informative, containing useful information missing in the original report); (b) equivalent to the original report; (c) satisfactory, but missing information that should have been included; and (d) unsatisfactory. RESULTS: The consultant graded 64 reports as more informative than the original, 687 as equivalent to the original, 32 as satisfactory, and two as unsatisfactory. The senior registrar considered 29 reports to be better than the original, 739 to be equivalent to the original, 15 to be satisfactory, and two to be unsatisfactory. The junior registrar found that 88 reports were better than the original, 681 were equivalent to the original, 14 were satisfactory, and two were unsatisfactory. Each judge found two different reports to be unsatisfactory according to their criteria. All 785 reports generated by the computer system received at least two scores of satisfactory or better. CONCLUSIONS: In this representative study, Professor Belmonte generated bone marrow reports that proved to be as accurate as the original reports in a large university hospital. The haematology knowledge contained within the system, the reasoning process, and the function of the software are safe and effective for assisting haematologists in generating high quality bone marrow reports.

Bone Marrow↗

Fanconi's anaemia presenting as acute myeloid leukaemia in adulthood.

We describe a 28-year-old male patient who presented with apparently de novo acute myeloid leukaemia (AML) who was subsequently found to have Fanconi's anaemia (FA). The gene for complementation group A (FAA) has recently been localized to chromosome 16q24.3 and utilizing genetic markers closely linked to this locus we were able to conclude that this patient was likely to belong to complementation group A. FA presenting as AML is an exceptionally rare event and all previously described cases have occurred in patients less than 21 years of age. We conclude that the diagnosis of FA should always be considered in younger patients presenting with AML. It is important that the correct diagnosis is made in these individuals because the administration of conventional chemotherapy may well have devastating consequences for them. Correlations between the specific mutations causing FA and clinical phenotypes are likely to become apparent as more genetic analyses are performed in this group of patients.

Adult↗

Guidelines for the management of thrombophilia. Department of Haematology, The Royal London Hospital, Whitechapel, London, UK.

Although there are numerous risk factors for venous thromboembolic disease, the term 'thrombophilia' refers only to those familial or acquired disorders of the haemostatic system that result in an increased risk of thrombosis. The inherited thrombophilias include antithrombin III deficiency, resistance to activated protein C (factor V Leiden), protein C and protein S deficiencies as well as some rare forms of dysfibrinogenaemia. It is possible that other inherited conditions might also predispose to thrombosis. In contrast, when using the above definition, the antiphospholipid syndrome is the only genuine acquired thrombophilic state. Patients who have thromboembolic disease at a young age with no provoking event or who have a positive family history or whose thrombosis involves an unusual site should be investigated for thrombophilia. The management of a patient identified as having a laboratory abnormality associated with thrombophilia will depend on a variety of factors such as the patient's individual and family thrombotic history, the site of the thrombosis and the presence of other prothrombotic risk factors. The use of prophylactic anticoagulation during pregnancy and the puerperium requires particularly careful consideration in thrombophilic women. As more becomes known about the thrombophilias it will become possible to formulate more exact guidelines as to the management of these conditions.

Adult↗

Adhesion molecule expression on CD34+ progenitor cells from normal and aplastic anaemia bone marrow.

Aplastic anaemia (AA) is a disease of bone marrow failure. Evidence has been produced for both a stem cell and a stromal cell defect in this disease. The contribution of deficient or defective cell adhesion molecules (CAMs) has not been determined. CAMs have been shown to be important in stem cell-stromal cell interactions and maintenance of haemopoiesis. In this study the expression of CAMs (LFA-1, LFA-3, ICAM-1. VLA-4, CD44, sLex and L-selectin) on CD34+ progenitor cells from 10 normal donors and eight patients with AA was investigated using double immunofluorescence. There was no significant difference in the percentage of CD34+ cells that were CAM+ between normal and AA bone marrow, suggesting that abnormal CAM expression on AA progenitor cells is not responsible for nor contributes to the pathogenesis of the disease. However, these findings do not exclude abnormal CAM function on progenitor cells, or abnormal expression or function of CAM ligands or counter-receptors on AA stromal cells.

Adult↗

A retrospective study of risk factors of akathisia in terminally ill patients.

Akathisia is a distressing disorder that manifests as a state of restlessness and motor agitation. We aim to highlight the problem of akathisia to the palliative care physician by identifying and quantifying risk factors in the terminally ill. A retrospective case-control study was utilized to investigate risk factors for akathisia. Medical records of cases (N = 100) and controls (N = 365) archived in a computerized database were downloaded and risk factors determined using conditional logistic regression analyses. Exposure to pharmacologically similar drugs, such as haloperidol [odds ratio (OR), 18.4; 95% confidence interval (CI), 8.2-41.4], prochlorperazine (OR, 8.1; 95% CI, 3.0-21.8), and promethazine (OR, 3.3; 95% CI, 1.3-8.0), conferred an increased risk. Other significant variables were exposure to morphine (OR, 5.3; 95% CI, 1.9-14.2), sodium valproate (OR, 2.5; 95% CI, 1.0-6.4), and sodium bicarbonate/tartrate (Ural) (OR, 4.2; 95% CI, 1.2-15.3). Highlighting factors that predispose patients to akathisia emphasizes that this syndrome should not be forgotten when treating the terminally ill. It is recommended that those drugs identified should be judicially used and carefully monitored.

Adult↗

Splenic sepsis in sickle cell disease.

We describe two patients with sickle cell disease (SCD) who developed infections situated in the spleen. One patient had a splenic abscess and there was strong clinical evidence for an infected splenic infarct in the second patient. SCD predisposes to splenic infection because of functional hyposplenism, defective phagocyte function and splenic infarction. Splenic infections can occur in patients who might be considered to have an absent spleen and the diagnosis of splenic abscess should be considered in individuals with SCD who present with fever and abdominal pain.

Abscess↗

SLe(x) expression of normal CD34 positive bone marrow haemopoietic progenitor cells.

We investigated sialylated Lewis x (sLe(x)) antigen expression on CD34 positive (CD34+) haemopoietic progenitors in the bone marrow of eight healthy volunteers using monoclonal antibodies. We found that in all the samples examined, CD34+ bone marrow progenitors strongly expressed the sLe(x) antigen. This contradicts previous publications which reported sLe(x) expression on malignant blast cells but not on normal CD34+ progenitor cells.

Antigens, CD↗

The binding of acute myeloid leukemia blast cells to human endothelium.

AML blast cell adhesion to endothelium is in all likelihood a prerequisite for blast cell migration across the vascular wall in the periphery and the subsequent establishment of leukemic extravascular disease. A general feature of malignant cells is their acquisition of altered or aberrant adhesive capabilities which appear to be associated with their ability to metastasize. Aberrant expression of integrin adhesion molecules and of membrane oligosaccharide structures is found in AML and various solid tumors. With respect to AML, these alterations in adhesive phenotype may confer a proliferative advantage on the malignant cells in the marrow, may facilitate egress from the bone marrow into the peripheral vasculature and may enable AML blast cells to traverse the vessel wall and so establish extravascular disease. Oncogenes may be directly involved in the acquisition of such aberrant adhesive phenotypes. Neutrophil extravasation is described as a model for leukocyte migration across the vessel wall and brief summaries of experimental work involving aspects of AML blast cell and normal CD34+ bone marrow cell adhesion to endothelium in vitro are described.

Acute Disease↗

Acute myeloid leukaemia blast cells bind to human endothelium in vitro utilizing E-selectin and vascular cell adhesion molecule-1 (VCAM-1).

The adhesion of acute myeloid leukaemia (AML) blast cells to human umbilical vein endothelial cells (HUVECs) was investigated in vitro. Adhesion of blast cells from 10 cases of AML to unstimulated and interleukin-1 beta (IL-1) stimulated HUVECs was similar to or greater than that of control neutrophils. The extent to which endothelial E-selectin and vascular cell adhesion molecule-1 (VCAM-1) were involved in this adhesive process was investigated using blocking monoclonal antibodies to these proteins. In the majority of cases studied (7/8), anti-E-selectin significantly inhibited adhesion to IL-1 stimulated endothelium (26-65% inhibition) and in 5/8 cases so did anti-VCAM-1 (maximum of 31% inhibition). All cases were found to express the sialylated Lewis x antigen and very late activation antigen-4, ligands for E-selectin and VCAM-1 respectively. Our results indicate that leukaemic blast cells adhere to human endothelium and that there are E-selectin and, to a lesser extent, VCAM-1-dependent components to this process. Such adhesive interactions are likely to confer on AML blast cells the ability to migrate across the vascular wall and so to establish extravascular disease.

Acute Disease↗

Plasma morphine-3-glucuronide, morphine-6-glucuronide and morphine concentrations in patients receiving long-term epidural morphine.

Plasma morphine concentrations were measured in five cancer patients receiving long-term epidural morphine administration. Peak concentrations were observed within 1 h of dosage and concentrations then declined biexponentially. Plasma morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations were measured in two patients and plasma M3G concentrations were observed to be much higher than plasma M6G and morphine concentrations. Peak plasma M6G concentrations occurred within 1.0 h of dosing and plasma M6G concentrations then remained higher than plasma morphine concentrations.

Analgesia, Epidural↗