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Biomedical subjects

H Brooks

Publications and source records attributed to H Brooks.

At least 37 records · Page 2Linked to original sources
PubMed1992

The three week sulphasalazine syndrome.

We report a 53-year-old man with sero-negative rheumatoid arthritis who developed a fever, rash and hepatitis 3 weeks after starting sulphasalazine therapy. This was associated with a T cell lymphocytosis, eosinophilia and evidence of classical complement pathway activation. He responded to high dose corticosteroids. This is a rare but characteristic reaction which is likely to be encountered by rheumatologists more frequently with the increasing use of sulphasalazine. It should be recognized promptly as it may be fatal and can be confused with other systemic diseases.

Arthritis, Rheumatoid↗
PubMed1983

Detection of cell surface and intracellular antigens by human monoclonal antibodies. Hybrid cell lines derived from lymphocytes of patients with malignant melanoma.

This study represents an initial attempt to analyze the humoral immune reactions of patients with malignant melanoma by hybridoma methodology. Using lymphocytes from regional lymph nodes, peripheral blood and tumor infiltrates, 158 fusions were performed with SKO-007 (human myeloma line), LICR-LON-HMy2 (LICR-2), GM 4672 (human lymphoblastoid lines), or NS-1 (mouse myeloma line). Fusion of lymph node lymphocytes with NS-1 resulted in a 3-4 times higher frequency of clones than fusion with LICR-2, and a 10 times higher frequency than fusion with SKO-007 or GM 4672. In the case of peripheral blood lymphocytes, fusion with NS-1 gave greater than 25 times higher frequency of clones than fusion with LICR-2 or SKO-007. Production of human mu, gamma, or alpha heavy chains was detected in 50-80% of wells containing growing clones, and the levels of immunoglobulin ranged from 0.3 micrograms to 40 micrograms/ml. NS-1-derived clones could be easily subcultured, while LICR-2 and SKO-007 clones grew more slowly on subculturing. In this study, Ig secretion appeared to be a more stable property of LICR-2-derived clones than NS-1-derived clones. A panel of 20 human cancer cell lines was used to screen 771 Ig-secreting cultures for antibody to cell surface or intracellular antigens. Reactivity with cell surface antigens was found infrequently (6 cultures), whereas reactivity with intracellular antigens was more common (27 cultures). A new cell surface antigen with properties of a glycolipid was defined with an IgM monoclonal antibody secreted by a tetraploid cell derived from a fusion of LICR-2 with lymphocytes from the axillary lymph node of a patient with melanoma. The hybrid cell line has been subcloned four times and secretes 5 micrograms IgM/ml. The antigen detected by this IgM antibody was found on 5 of 23 melanoma cell lines and 12 of 30 epithelial cancer cell lines. No reactions were found with 11 cultures derived from normal cells. Stable cell lines secreting human antibody that detected nuclei, nucleoli, cytoskeletal elements, Golgi complex, or other cytoplasmic components were also isolated in this study. One of these antibodies detected an intracellular antigen that is restricted to cells of neuroectodermal derivation, and a second antibody reacted primarily with cells of epithelial origin. Using these methods to isolate and analyze human monoclonal antibody, it should now be possible to define the repertoire of the humoral immune response to melanoma.

Animals↗
PubMed1982

Mechanism of abnormal motion of the posterior leaflet in mitral stenosis.

Echocardiographic visualization of diastolic anterior motion of the posterior leaflet has proven to be diagnostic of mitral stenosis. In order to elucidate the mechanisms which underlie this finding and to explain why it is absent in some proven instances of mitral stenosis, we analyzed leaflet motion as a function of torque and derived a theoretic expression which permitted us to predict the direction of leaflet motion in mitral stenosis in terms of degree of commissural fusion and leaflet dimensions. The analysis was tested in an experimental model consisting of an isolated, perfused pig heart. Dimensions and degree of fusion of mitral valve leaflets were varied surgically in 5 specimens. Corresponding values proportional to torque were computed for each leaflet and the associated modifications of valve motion recorded cinematographically through a fiberscope inserted into the left ventricular cavity. The theoretical considerations indicated that, when leaflet commissures are fused, diastolic movement of the posterior leaflet is determined by the torques on both leaflets and that the relative length (base to free edge) of the leaflets is the major determinant of the direction of the resultant displacing force. The posterior leaflet may move posteriorly early in diastole until this motion is restricted by the fusion, but anterior motion of both leaflets results when the anteriorly directing force becomes dominant. Anterior motion of the posterior leaflet therefore occurs when leaflet fusion is extensive and the anterior leaflet remains longer than the posterior. Posterior motion of the posterior leaflet tends to occur with leaflet fusion, even in severe or moderate mitral stenosis, when the ratio of anterior to posterior leaflet length approximates unity. Direct observations of leaflet motion in the perfused porcine hearts confirmed these relationships.

Animals↗
PubMed1977

TQ-ST segment mapping: critical review and analysis of current concepts.

Controversy and confusion surround many aspects of TQ-ST segment mapping today. Technical standards pertaining to the recording and measurement of the TQ-ST deflection have not been uniformly established nor has the correlative value of the deflection as an indicator of myocardial injury been clearly ascertained. The TQ-ST deflection is believed to originate primarily although not exclusively as a result of extracellular potassium accumulation in the ischemic region and subsequent establishment of a transmembrane potential gradient during diastole and systole at the ischemic boundary. Nonspatial factors (including electrolytes, antiarrhythmic agents, heart rate) influence the TQ-ST deflection by altering this gradient. Spatial factors (including ischemic area and shape, electrode location) alter the relative position of the ischemic boundary to the electrode site and as such can be analyzed with the solid angle theorem. Further study of the complex behavior of the TQ-ST segment deflection, particularly in the presence of pharmacologic intervention, is necessary before mapping techniques can be used reliably in clinical studies designed to quantitate and modify ischemic damage.

Coronary Disease↗
PubMed1977

Early changes in contractility and coronary blood flow in the normal areas of the ischemic porcine heart.

The regional responses of normal myocardium distant from an ischemic area were studied during acute anterior descending occlusion in the open-chest chloralose-anesthetized pig. Three markers of regional response in both normal and ischemic areas were used: surface ECG electrode, a force gauge in series with left ventricular outer wall fibers, and coronary blood inflow to each region as determined by electromagnetic cuff-probes. Following brief anterior descending artery occlusion (120 sec)., a characteristic rapid decline in contractile force and evolution of TQ-ST segment changes was observed in the ischemic area. In contrast, in the distant area increases in contractil force (p less than 0.001) and coronary blood flow (p less than 0.002) occurred. These distant responses were essentially obliterated following transection and cannulation of the artery supplying this region (p less than 0.05). The findings are consistent with a reflex neurovascular mechanism operating within the intact heart. This reflex is rapidly activated in order to maintain adequate levels of cardiac performance despite sudden loss of functional myocardial mass.

Animals↗
PubMed1977

Right ventricular performance during ischemia: an anatomic and hemodynamic analysis.

This study in the pig was designed to characterize right ventricular (RV) contractile responses during infarction involving three areas of the heart--anteroseptal, anterolateral, and inferoseptal. Porcine coronary architecture was studied from multicolor vinyl casts. Distribution of blood supply to ventricular myocardium and papillary muscles was defined by intra-arterial dye injection. High-fidelity pressure and flow data were measured simultaneously in both ventricles following ligation of approximately equal lengths of the anterior descending, left circumflex, or posterior descending arteries. In the three groups, weight of myocardium involved by the occluded artery was comparable and there was significant depression of left ventricular performance, more pronounced in the two anterior infarcts. However, in anterolateral infarction, despite the obligatory drop in RV flow, there was no significant alteration in RV end-diastolic pressure (EDP), peak rate of rise of RV pressure (dP/dt), or time-to-peak developed dP/dt. In contrast, with both anteroseptal and inferoseptal infarctions there were significant alterations in all RV contractile parameters, at increased levels of RVEDP, signifying a primary depression in RV contractile state. With inferoseptal infarction, further occlusion of the right coronary near its origin produced a more exaggerated and selective RV contractile abnormality and, in half of the animals, varying degrees of acute tricuspid insufficiency.

Animals↗
PubMed1977

Spatial and nonspatial influences on the TG-ST segment deflection of ischemia. Theoretical and experimental analysis in the pig.

Spatial and nonspatial aspects of TQ-ST segment mapping were studied with the solid angle theorem and randomly coded data from 15,000 electrograms of 160 anterior descending artery occlusions each of 100-s duration performed in 18 pigs. Factors analyzed included electrode location, ischemic area and shape, wall thickness, and increases in plasma potassium (K(+)). Change from control in the TQ-ST recorded at 60 s (DeltaTQ-ST) was measured at 22 ischemic (IS) and nonischemic (NIS) epicardial sites overlying right (RV) and left (LV) ventricles. In IS regions, DeltaTQ-ST decreased according to LV > septum > RV and LV base > LV apex. In NIS regions, LV sites had negative (Neg) DeltaTQ-ST which increased as LV IS border was approached. However, RV NIS had positive (Pos) DeltaTQ-ST which again increased as RV IS border was approached. With large artery occlusion IS area increased 123+/-18%, DeltaTQ-ST at IS sites decreased (-38.1+/-3.6%), and sum of DeltaTQ-ST at IS sites increased by only 67.3+/-10.3%. In RV NIS Pos DeltaTQ-ST became Neg. With increased K(+), DeltaTQ-ST decreased proportionately to log K(+) (r = 0.97+/-0.01) at IS and NIS sites on the epicardium and precordium. TQ-ST at 60 s was obliterated when K(+) = 8.7+/-0.2 mM. All findings were significant (P < 0.005) and agreed with the solid angle theorem. Thus, a transmembrane potential difference and current flow at the IS boundary alone are responsible for the TQ-ST. Nonspatial factors affect the magnitude of transmembrane potential difference, while spatial factors alter the position of the boundary to the electrode site.

Animals↗
PubMed1976

The QRS complex during myocardial ischemia. An experimental analysis in the porcine heart.

Although ST segment deflections have been widely utilized as a means of assessing the degree of underlying ischemic injury, the relationship of QRS complex alterations to the ischemic process is poorly understood. In this study we made a beat-to-beat analysis of the QRS complex in terms of ventricular activation time (CT) and R wave voltage (V) in the acutely ischemic porcine myocardium and analyzed the relationship of these responses to changes in the area of ischemic involvement, altered myocardial energy demands, and plasma [K+]0 levels. With the onset of ischemia the QRS complex underwent a specific and reproducible biphasic sequence with an initial decrease in CT and V indicating a transient increase in the conduction velocity of the ischemic tissue. Subsequently both CT and V returned briefly to control and then increased dramatically, now indicating a marked decrease in conduction velocity. The time when CT first began to increase (Tc) was shortened by enlarging the area of ischemia or after an inotropic intervention and was lengthened by decreasing the area of ischemia or with administration of propranolol. Moreover Tc was found to be inversely proportional to plasma [K+]0 in the range 3.4-8.8 mM, above which the initial decrease in CT and V was no longer present. We conclude that this biphasic sequence of QRS alterations in early myocardial ischemia is attributable to a progressive leakage of potassium out of the ischemic cells which in turn alters both the time-course and transmural pathway of the activation process through the ischemic tissue. These changes are related to both inotropic state and the area of ischemic involvement.

Animals↗
PubMed1976

The contribution of anticoagulants to platelet dysfunction with extracorporeal circulation.

This investigations evaluates the effects of anticoagulants on platelet function. Fresh human blood from 40 nonmedicated volunteers was anticoagulated with 4.3 units per milliliter heparin and/or acid-citrate-dextrose (ACD) solution 1:9. Retention of platelets from whole blood on glass beads was performed by the method of Bowie. Platelet retention of heparinized blood averaged 88.1 +/- S.E. 1.5 per cent; ACD platelets averaged 24.6 +/- S.E. 2.8 per cent. Platelet retention with citrate-phosphate-dextrose (CPD) and ethylenediaminetetraacetic acid (EDTA) yielded 26.0 +/- S.E. 3.9 per cent and 19.1 +/- S.E. 7.5 respectively. The addition of ACD to heparinized blood decreased platelet retention (19.7 +/- S.E. 3.1 per cent). The addition of heparin to ACD or CPD blood did not alter the original decreased retention. Calcium added, even in excess, to blood containing heparin and ACD did not reverse the depressed retention (29.3 +/- S.E. 4.6 per cent). The substitution of CPD gave similar results. With mixtures of separately collected ACD and heparininzed blood, depression of platelet retention was directly proportional to the amount of ACD blood present. Altering the pH of the ACD blood did not affect its depressed retention of platelets. Neutralizing heparinized blood 50 per cent with protamine or Polybrene also significantly depressed platelet retention 34.6 +/- S.E. 5.8 per cent and 35.5 +/- S.E. 4.0 per cent, respectively. Neither protamine nor Polybrene had any effect upon ACD blood. These data indicate that anticoagulants may play a significant role in the depressed platelt function observed during and following extracorporeal circulation.

Anticoagulants↗
PubMed1975

Biventricular dynamics during quantitated anteroseptal infarction in the porcine heart.

The porcine heart has been shown to have close anatomic similarity to the human heart and was used as the experimental model in this study to gain further understanding of the early responses of both ventricles during acute anteroseptal myocardial infarction. High fidelity pressure and flow data were measured and multiple preejection and ejection variables were calculated for both ventricles. Infarct weight and distribution in both ventricles were quantitated. The standard infarction resulted from single stage ligation of the left anterior descending coronary artery just beyond its midpoint and second left ventricular branch. It comprised an average of 15.8 percent of total ventricular myocardium with an infarct/perfused ratio of 0.62 and a periinfarction transition zone of 7.5 mm, and involved significant portions of both ventricles and the interventricular septum. Performance characteristics of both ventricles were altered significantly by anteroseptal infarction and involved all phases of contraction--end-diastole, isovolumic systole and ventricular ejection. Although contractile alterations in the right ventricle were significant, they were somewhat delayed, yielding relatively low correlation coefficients with analogous left ventricular contractile indexes. These correlations became quite distinct during specific ventricular stresses. Comparison of anterolateral and anteroseptal infarction, matched in terms of infarct size, indicated that the right ventricular changes in the latter were related to direct involvement of the right ventricular free wall and septum rather than secondary to left ventricular alterations.

Acute Disease↗
PubMed1975

Precordial and epicardial surface potentials during Myocardial ischemia in the pig. A theoretical and experimental analysis of the TQ and ST segments.

The solid angle theorem was used to analyze the relationships between TQ and ST segment deflections recorded from precordial and epicardial locations and the time course, size, shape, and transmural location of the ischemic process in the ventricular myocardium. Mathematical predictions were compared with experimental data from the intact heart. Precordial electrograms obtained in anesthetized close-chest pigs were compared with epicardial electrograms recorded directly from the heart's surface. Various areas of ischemia were produced by occluding large and small coronary artery branches, and the resultant changes in ischemic shape were delineated with Thioflavin S injections and postmortem ultraviolet photography. Formally derived equations and cumulative experimental data were in close agreement, suggesting that in the ischemic ventricle (1) TQ depression always accompanies ST elevation, (2) TQ and ST segment changes in magnitude and polarity are complex functions of ischemic size, shape, and transmural location; (3) precordial electrocardiogram (ECG) ST segment elevation is directly related to ischemic size; and (4) epicardial ECG ST segment elevation is inversely related to ischemic size. It is thus concluded that precordial and epicardial ECG TQ and ST segment deflections are complex functions of ischemic geometry and that their accurate interpretation with respect to ischemic size and shape and in the presence of pharmacological interventions is often difficult and may be misleading.

Action Potentials↗
PubMed1975

Denatured plasma and platelet function.

Thrombocytopenia and platelet dysfunction are well known complications of extracorporeal circulation. The production of ""denatured'' protein is a common occurrence with extracorporeal circulation even in the absence of a blood-gas interface. We subjected platelet-poor plasma to vigorous bubbling with air and studied the effect of this ""denatured'' plasma on platelets from the same donor. Aggregation induced by ADP, epinephrine or collagen was measured. The bubbled plasma decreased the delay in the onset of aggregation observed with collagen and eliminated the biphasic aggregation response induced by epinephrine. These data indicate that ""denatured'' protein may affect platelet function and may play a role in the thrombocytopenia and altered platelet function associated with extracorporeal circulation.

Adenosine Diphosphate↗
PubMed1975

Myocardial ultrastructure and function during progressive early ischemia in the intact heart.

Regional contraction of ischemic anterior and normal lateral left ventricular myocardium was measured with isometric force gauges after 5, 10, 15, and 20 minutes of anterior descending coronary artery occlusion-each followed by 10 minutes of reperfusion. Multiple myocardial biopsies of both regions were taken at these same intervals and examined by electron microscopic techniques. Mean contraction of the ischemic area fell significantly in 15 to 30 seconds and returned to an average of 68, 51, 40, and 28 per cent, respectively, after 5, 10, 15, and 20 minutes of ischemia. Simultaneously, focal morphologic changes were detected after 5 and 10 minutes, were more clear and widespread at 15 minutes, and diffuse and unequivocal at 20 minutes, when return of local contraction was minimal. The changes of myocardial morphology in the ischemic area as seen by electron microscopy were: reduced content of glycogen granules and mitochondrial changes. The latter began to appear at 5 minutes and consisted of swelling, disruption of cristae, and reduction of matrix. This study indicates a qualitative correlation between ultrastructural changes in regionally ischemic myocardium and diminished regional function in the intact heart. At 5 and 10 minutes the mitochondrial changes were focal, requiring multiple samples, while at 15 and 20 minutes they became more widespread, making the occasional sample more representative.

Animals↗
PubMed1975

Myocardial ultrastructure and contraction during short periods of experimental ischemia.

The relationship of structure and function of the intact myocardium during the early minutes of experimental ischemia was studied in the anesthetized, open-chest pig. Regional contraction of ischemic and normal myocardium was measured, using isometric strain gauges on the anterior and lateral left ventricle. Biopsies for electron microscopy were taken consecutively 5, 10, 15, and 20 minutes after anterior descending artery occlusion-each followed by 10 minutes of reperfusion. Contraction of the ischemic area fell significantly within 15 to 30 seconds following occlusion, returning to 68, 50, 40, and 28%, respectively, after 5, 10, 15, and 20 minutes fo ischemia. In contrast, slight morphological changes were detected only after 5 and 10 minutes of ischemia, becoming more clear after 15 minutes, and unequivocal after 20 minutes-when return of contraction was minimal. The morphologic alterations in the ischemic area as seen by electron microscopy were: reduction of glycogen granules and specific changes in the mitochondria. The latter, consisting of swelling, disruption of cristae, and reduction of matrix, began to appear at 5 minutes and were more evident after 10 minutes of ischemia. These changes, although present, were not always proportional to sequential ischemic periods. This apparent lack of correlation between contraction and morphology could be due to sampling problems or to the focal nature of the ischemic process. However, it could imply that the changes seen by electron microscopy are a "late" phenomenon as compared to the loss of function. Morphologic corroboration of the immediate decrease of contraction of ischemic myocardium still escapes the perception of current morphological techniques. It is hoped that more refined stereological measurements will help bridge the present gap between function and morphology in early myocardial ischemia.

Animals↗