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Biomedical subjects

A J Bell

Publications and source records attributed to A J Bell.

At least 55 records · Page 3Linked to original sources
PubMed1991

Preliminary studies for an immunotherapeutic approach to the treatment of human myeloma using chimeric anti-CD38 antibody.

Multiple myeloma is a disease in which conventional chemotherapy has only limited value, but which may be ideal for treatment with passive antibody against a suitable cell surface antigen on the neoplastic plasma cell. The CD38 antigen is known to be present on the majority of neoplastic plasma cells, and this was confirmed by detailed examination of bone marrow aspirates from three patients. Strong expression of CD38 was confined to cells which, by the criteria of light-scattering profiles and possession of cytoplasmic Ig, were plasma cells. The vast majority of neoplastic plasma cells appeared to be involved. Using a cell line as a model, it was found that the CD38 antigen acts as a target for a chimeric antibody prepared from the antibody OKT10. The chimeric antibody consists of the Fab portion of the mouse monoclonal antibody linked by a stable thioether bond to an Fc molecule derived from human IgG1, thereby forming mouse Fab-human Fc. In contrast to the parent antibody, the chimeric molecule mediates antibody-dependent cellular cytotoxicity (ADCC) very efficiently with human blood mononuclear effector cells, and is effective at low concentration. Also, even though the CD38 antigen is present on natural killer cells, there appears to be little deleterious action of the antibody on effector cell function. The antibody also failed to affect the growth of progenitor cells of the granulocyte/macrophage or erythroid lineages present in normal bone marrows, despite the suspicion that these cells express the antigen. Other advantages of the CD38 molecule are that it is not found in the serum of patients with myeloma, and it does not appear to modulate in vitro. Fourteen patients with florid myeloma and on various chemotherapeutic regimes had an undiminished capacity to mediate ADCC with the chimeric antibody, when compared with normal individuals. The maintenance of ADCC activity, coupled with the known suppression of the antibody response in these patients, augers well for treatment with chimeric antibody.

ADP-ribosyl Cyclase↗
PubMed1991

Red cell aplasia in myelodysplastic syndrome.

Six cases of red cell aplasia occurring in patients with myelodysplastic syndromes (MDS) showed a diversity of clinical course and prognosis. In some patients red cell aplasia may have represented an evolution of MDS while in others autoimmune destruction of erythoblasts may have been the mechanism. A proliferative phase is seen in many of these patients, the clinical importance of which is uncertain.

Aged↗
PubMed1990

Importance of the great vessels in the genesis of the electrocardiogram.

The electrocardiogram is the graphic representation against time of the difference in potential between points of the body caused by the current field of the heart. To examine the origin of this current field, a method of transforming body surface electrocardiographic data to the epicardial surface has been developed. The computed epicardial current density distributions in 219 patients with acute inferior myocardial infarction showed that, in 89% of patients, the current flow out of the heart during the ST segment came from two regions, not only from the infarction region but also from a region over the great vessels. This findings suggests that current flows from the ischemic region, through the low-resistance pathway provided by the intracavity blood, out the great vessels, and back to the epicardium. A similar pathway has been hypothesized when ischemia caused endocardial ST elevation, such as during a stress test or with unstable angina. To test this hypothesis, a group of patients with ST depression on the 12-lead electrocardiogram, not associated with ST elevation, was examined with body surface mapping. Ninety-four percent of patients had epicardial current density distributions that showed a region of current flow out of the heart and over the great vessels that was consistent with this hypothesis. This could explain the poor localization of coronary artery disease by electrocardiographic techniques when there is ST depression on the body surface.

Aorta↗
PubMed1989

Prognostic significance of ST potentials determined by body surface mapping in inferior wall acute myocardial infarction.

Electrocardiographic body surface mapping on admission to coronary care has been shown to predict prognosis in a previous study of 100 patients with inferior wall acute myocardial infarction (AMI). A further 98 patients with first inferior wall AMI were now studied by body surface mapping on admission to coronary care to confirm that both the spatial distribution or map pattern of ST-segment potentials and the precise measurement of the maxima and minima are of prognostic significance. Each ST-segment map was compared by correlation coefficient to the average map pattern of the 4 groups derived in a previous study and placed in the group with the highest correlation coefficient. Analysis of these groups against outcome confirmed that the group dominated by a large area of marked anterior ST depression was associated with a high rate of complications and a significantly lower survival free of coronary artery bypass grafting (p less than 0.01). Patients in this group had more extensive and severe coronary artery disease than patients in the other groups. Increasing values of maximal ST depression correlated with mortality and complication rates. The extent by which the magnitude of ST-segment depression exceeded the magnitude of ST-segment elevation correlated with mortality and incidence of left ventricular failure. The results confirm the findings of the original study. Body surface mapping is of prognostic significance in inferior wall AMI.

Adult↗
PubMed1989

Natural history of ST-segment potential distribution determined by body surface mapping in patients with acute inferior infarction.

The authors studied the natural history of the electrocardiographic ST-segment using body surface mapping in 123 patients with acute inferior infarction who were not treated with thrombolytic agents. In 91 patients they compared body surface ST-segment maps recorded at 7.9 +/- 5.4 hours after the onset of acute myocardial infarction with maps recorded at 32.6 +/- 21.6 hours after infarction. In 46% of the patients the ST-segment distribution map pattern was unchanged. Twenty-eight percent of the patients moved to a ST-segment distribution associated with low mortality, and 7% correlated with a normal ST-segment distribution. Patients who started in a group dominated by marked anterior ST-segment depression or who developed this pattern at the time of the late map had a 45% morbidity, compared to 13% for patients who never developed this pattern (p less than 0.005). In a second group of 61 patients they compared maps recorded at 15.0 +/- 15.8 hours after infarction and repeat maps 19.6 +/- 13.0 recorded months later. At follow-up mapping, 44% of the patients correlated with a normal ST-segment distribution, 38% of patients had a low-risk pattern map and in 7% the map pattern was dominated by anterior ST-segment potential depression. The latter patients had a higher morbidity than patients in the other groups, but this did not reach statistical significance. Four of seven patients in this last group had significant angina at the time of follow-up mapping, compared to 2 of 54 patients in the other two groups (p less than 0.001).

Aged↗
PubMed1989

The relationship of ST elevation to eventual QRS loss in acute inferior myocardial infarction.

The electrocardiographic changes of ST-segment elevation in acute myocardial infarction are related to the region of infarction. The authors examined body surface map data in 70 patients with acute inferior infarction to determine the exact relationship of the initial ST elevation to the eventual loss of QRS. The patients had no evidence of previous myocardial infarction and no subsequent infarction and did not receive thrombolytic therapy or other acute interventions, such as surgery. Maps were recorded on admission to the hospital, during the hospital admission and again at follow-up examination 6-48 months after infarction. The region of ST elevation of the initial body surface map was compared to a QRS loss region derived by subtracting the follow-up map, integrated over the 80 msec after the onset of the QRS, from a "QRS loss region" derived from 381 normal patients using the same interval. In 76% of patients there was a direct relationship between the position of the ST elevation and the QRS loss region (mean correlation coefficient, 0.49). In a further 15% of patients there was a general relationship without specific features, and in the remaining 8% the difference maps were not related to the position of ST elevation. The region of ST elevation predicts the eventual QRS loss in the majority of patients and may be useful for monitoring interventions in acute myocardial infarction.

Aged↗
PubMed1989

Derived epicardial potentials differentiate ischemic ST depression from ST depression secondary to ST elevation in acute inferior myocardial infarction in humans.

It was hypothesized that in acute inferior wall myocardial infarction, an additional ischemic area in the subendocardium of the noninfarcting territory would produce a selective current dipole between the infarcting and ischemic regions. A resistance network model to calculate epicardial potentials from body surface electrocardiographic potentials was developed and used to examine the hypothesis in 219 patients with acute inferior myocardial infarction. In the learning set of 110 patients, two characteristic dipole patterns were observed, each associated with a high mortality rate in the ensuing 15 months when compared with that in the remaining patients. In the test set of 109 patients, a double-blind analysis of the patterns showed that the 34 patients with a dipole pattern had a collective mortality rate of 35% at 15 months compared with a 15 month rate of 5% in the remaining patients. In the total group of 219 patients, the magnitude of ST segment elevation and both the magnitude and integral of the area voltage of ST depression on the epicardium were significantly correlated with the mortality rate (p less than 0.0002 for all variables against death at 15 months). This study strongly suggests that ST depression due to ischemia can be differentiated from ST depression secondary to the ST elevation in acute inferior infarction by the examination of epicardial potential distributions.

Aged↗
PubMed1987

Peripheral blood stem cell autografts in the treatment of lymphoid malignancies: initial experience in three patients.

Large numbers of circulating haemopoietic progenitor cells were collected from three patients with lymphoid neoplasms for the purpose of haemopoietic reconstitution following intensive chemotherapy or chemoradiotherapy. Each patient underwent four to six leukaphereses at a time when the circulating stem cell pool was expanded. 2-3 weeks after the end of myelosuppressive chemotherapy. The peripheral blood mononuclear cells (PBMNC) thus obtained were assayed for granulocyte-macrophage colony-forming cells (CFU-GM) and were cryopreserved in liquid nitrogen. Two patients were autografted with PBMNC containing 60 X 10(4) and 76 X 10(4) CFU-GM/kg body weight respectively. Both these patients showed prompt engraftment which is stable at +10 and +6 months. A third patient who was autografted with PBMNC containing 33 X 10(4) CFU-GM showed only temporary and incomplete engraftment. These observations confirm that the peripheral blood may be used as a source of haemopoietic stem cells for autografting, but criteria for predicting engraftment are at present uncertain.

Adolescent↗
PubMed1987

Spatial distribution and prognostic significance of ST segment potential determined by body surface mapping in patients with acute inferior myocardial infarction.

We investigated the mechanism and significance of ST segment changes in inferior infarction by studying 100 patients with acute inferior infarction in whom body surface maps were recorded on admission. The magnitude of the maximum ST segment elevation (denoted Vmax) and magnitude of the maximum ST segment depression (denoted Vmin), as well as the ST depression on the standard 12-lead electrocardiogram were analyzed against morbidity and mortality (at a median follow-up time of 14 months). A value obtained by subtracting Vmax from Vmin correlated (p less than .0002) with outcome. Correlations were also found between Vmin and complications, Vmin and mortality, and between increasing levels of ST depression on the 12-lead electrocardiogram and mortality. The maps were also studied by grouping the 100 ST segment map patterns into five groups by cluster analysis techniques. One group showed marked anterior negativity and had 37% mortality compared with an overall 5% mortality for the remaining groups. The limited arteriographic and autopsy data available indicated that the findings of a diseased artery or arteries corresponded with the results of mapping. The mean map patterns of the five groups showed that, in most patients with inferior infarction, the standard chest leads V1 to V6 are over a region of steep voltage gradient. Small changes in the position of the standard chest lead can cause large changes in the displayed potentials. This study indicates that patients at high risk after acute inferior infarction can be identified by surface mapping on admission to the coronary care unit.

Electrocardiography↗
PubMed1986

Circulating stem cell autografts.

The role of autologous bone marrow transplantation in the treatment of malignant disease is currently being evaluated. The peripheral blood represents an alternative source of haemopoietic progenitors and the use of circulating rather than bone marrow stem cells permits autografting in patients with infiltrated bone marrows. It may also offer a lower risk of tumour contamination, although this is not yet proven. Several autografts using circulating stem cells (CSCs) have recently been reported. These are reviewed and current uncertainties and future prospects are discussed.

Animals↗
PubMed1986

Reversal of coagulopathy in Kasabach-Merritt syndrome with tranexamic acid.

An infant with a giant cavernous haemangioma developed a severe consumption coagulopathy and systemic bleeding. Replacement therapy with cryoprecipitate produced only a transient improvement in the abnormal clotting, but the addition of tranexamic acid resulted in sustained correction, permitting corrective surgery to be performed.

Afibrinogenemia↗