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Biomedical subjects

E Abraham

Publications and source records attributed to E Abraham.

At least 181 records · Page 10Linked to original sources

The effects of hemorrhage and trauma on interleukin 2 production.

Sepsis remains the major cause of postresuscitation death after hemorrhage and trauma. The high incidence of infection in this setting has been attributed to host defense abnormalities, including dysfunction in cell-mediated immunity. To elucidate the interaction between injury and host defense mechanisms, we measured interleukin 2 (IL 2) production by peripheral blood mononuclear cells in 21 patients immediately after unanesthetized, accidental hemorrhage or trauma. Interleukin 2 production in minimally injured patients (0.63 +/- 0.14 [SEM] units) was similar to that found in control, uninjured subjects (0.68 +/- 0.17 units). Compared with control patients, IL 2 production was reduced 56% in patients with moderate injury and 85% in patients with severe injury. There was significant correlation between the severity of injury and the reduction in IL 2 production. Lymphocyte proliferative response to phytohemagglutinin was reduced in patients with moderate and severe injury, and the reduction in proliferative response was significantly correlated with injury severity. These results indicate that marked abnormalities in cell-mediated immune function, as determined by IL 2 production, occur immediately after hemorrhage and accidental injury.

Adolescent↗

Immunologic mechanisms underlying sepsis in the critically ill surgical patient.

This article describes the range of immunologic abnormalities that follows accidental and operative trauma. The high rate of infection in critically ill postoperative patients may result from these abnormalities in host defense function. Means to recognize and correct the post-trauma immune deficiencies are discussed.

Anesthesia↗

Continuous monitoring of tissue pH with a fiberoptic conjunctival sensor.

To assess the relationship between conjunctival pH (pHcj), arterial pH (pHa), and cardiorespiratory variables during normal and low-flow conditions, hemorrhagic hypotension was induced in eight dogs. Conjunctival pH became significantly less than control values after a hemorrhage volume of 15 mL/kg (P less than .05); mean arterial pressure (MAP) did not fall until blood loss was 20 mL/kg. There was poor correlation between pHcj and pHa, cardiac index (CI), or MAP. There was a high degree of correlation, however, between pHcj-pHa difference (delta pH) and MAP (r = -0.886), CI (r = -0.846), and tissue oxygen extraction ratio (r = .896). The results of these experiments indicate that pHcj is a sensitive monitor of peripheral tissue perfusion, and that the degree of physiologic compromise associated with hemorrhage can be determined by analysis of the difference between arterial and conjunctival pH.

Animals↗

Hemodynamic and oxygen transport patterns in surviving and nonsurviving postoperative patients.

Invasive hemodynamic monitoring was performed on 220 critically ill surgical patients judged by clinical evaluation to have a high likelihood of surgical complications or death. Patients with markedly abnormal preoperative hemodynamic values were excluded from analysis. Data were separated into preoperative, intraoperative and postoperative time intervals and the mean value of each variable for each patient at each time period was computed. In comparison to survivors, the nonsurvivors generally had: (a) reduced myocardial performance as judged by lower cardiac index and left ventricular stroke work in the presence of high right and left ventricular filling pressures, (b) reduced pulmonary function (increased alveolar-arterial oxygen content difference and pulmonary shunt fraction), (c) pulmonary vasoconstriction (increased pulmonary artery pressure and pulmonary vascular resistance), and (d) decreased oxygen delivery despite maintenance of normal arterial blood gases and comparable hemoglobin values. Both survivors and nonsurvivors had vital signs usually within the normal range (until the terminal state of nonsurvivors).

Adult↗

The effects of hemorrhage on mitogen-induced lymphocyte proliferation.

Bacterial infection often occurs after trauma and hemorrhage and is believed to be a reflection of a compromised host defense system. In the present study, the effect of temporary loss of blood on lymphocyte proliferative capacity was investigated. Hemorrhage was induced in unanesthetized rats with chronically catheterized carotid arteries. Two hours after withdrawal of 30% of total blood volume, phytohemagglutinin-induced lymphocyte proliferation was almost completely suppressed; proliferation remained depressed for at least 24 hrs. The degree of suppression in lymphocyte proliferation was found to be dependent on the duration of hemorrhage. Mitogen-induced proliferation of lymphocytes was significantly reduced as early as 30 min after hemorrhage and became more depressed at 2.0 hr after hemorrhage. This abnormality in host defense mechanisms may contribute to the increased incidence of sepsis present after trauma and hemorrhage.

Animals↗

Cardiorespiratory patterns in severe delirium tremens.

To define the hemodynamic and oxygen metabolism patterns associated with severe delirium tremens, we examined cardiorespiratory variables in five patients over the 24 hours before (control), at the time of (delirium tremens), and during the 24 hours after resolution of (postresolution) delirium tremens. In comparing the delirium tremens period with the control period, significant increases were found in mean +/- SD cardiac index (4.9 +/- 1.7 L/min X sq m vs 3.6 +/- 0.7 L/min X sq m), left cardiac work index (6.4 +/- 2.4 kg X m/sq m vs 5.0 +/- 1.7 kg X m/sq m), oxygen delivery (681 +/- 204 mL/min X sq m vs 546 +/- 176 mL/min X sq m), and oxygen consumption (204 +/- 38 mL/min X sq m vs 165 +/- 16 mL/min X sq m). Values for the control and postresolution periods were not significantly different. These results demonstrate that a hyperdynamic cardiorespiratory state is present during delirium tremens; this increased cardiac output may be a compensatory hemodynamic response to increased oxidative metabolism that requires additional therapeutic support.

Adult↗

Stimulation of human endothelial cell prostacyclin synthesis by select leukotrienes.

Cultured endothelial cells from human umbilical cord labeled with [3H]20:4 release radiolabel when exposed to leukotrienes C or D (LTC or LTD). The major radiolabeled 20:4 metabolite recovered in the culture medium was prostacyclin. Both leukotrienes produced a dose-dependent synthesis of prostacyclin, with a maximal response at 10(-7) M leukotriene. LTC promoted a twofold greater response than did LTD at all concentrations tested (10(-9) to 10(-7) M). In contrast, no release of radiolabel above basal levels was evident with a challenge of LTE or LTB at the same concentrations. Endothelial cells metabolize approximately 40-50% of exogenously supplied LTC to LTD and LTE in 60 min. Levels of alpha-glutamyltranspeptidase (gamma-GTPase), the ectoenzyme reported to convert LTC or LTD, were detected in intact endothelial cells with the chromogenic substrate L-gamma-glutamyl-p-nitroanilide at levels sufficient to account for the observed rate of LTC metabolism. High concentrations of the gamma-GTPase inhibitors, glutathione and AT-125, blocked the metabolism of LTC by endothelium. These results suggest that degradation of leukotrienes by endothelium may be one mechanism for inactivation of these lipid mediators.

Arachidonic Acid↗

Cardiorespiratory effects of pneumatic trousers in critically ill patients.

Although pneumatic antishock trousers (PT) are widely used in prehospital and emergency care, little is known about their cardiorespiratory effects in critically ill patients. To examine this issue, we measured hemodynamic and oxygen metabolism variables in ten critically ill patients. All patients were studied with PTs uninflated, after five minutes of PT inflation to 40 mm Hg, and five minutes after PT deflation. Significant increase in mean arterial pressure, systemic vascular resistance, and pulmonary artery pressures were present after PT inflation. No significant changes in cardiac index, stroke index, arterial or mixed venous blood gas values, or oxygen delivery were found. There was a downward trend in VO2 that was on the border of statistical significance. Regression analysis of cardiorespiratory variables on blood volume demonstrated no physiologic effects of external counterpressure in hypovolemic, hypervolemic, or normovolemic patients. We concluded that PT inflation increases BP through its effects on peripheral resistance. No significant autotransfusion effect was present, and there was a suggestive impairment in oxygen metabolism.

Adult↗

Effects of hemorrhage on inflammatory response.

Bacterial infection often occurs after trauma and hemorrhage and is believed to be a reflection of a compromised host defense system. In the present study, we investigated the effect of the temporary loss of blood on the integrity of the inflammatory response. Hemorrhage was induced in rats that had long-term carotid artery catheterizations and the autologous blood was returned to the animals two hours later. The development of carrageenan-induced inflammation was suppressed after the temporary loss of blood in a volume-dependent manner. After the withdrawal of 30% of the total blood volume the inflammatory response was decreased 82%, and remained suppressed for at least 24 hours. The degree of depression of the inflammatory response also was found to be dependent on the time elapsed before retransfusion. Vasoconstriction induced by hypovolemic stress does not appear to be the cause of the posthemorrhage suppression in inflammatory response.

Animals↗

The cyclooxygenase and lipoxygenase activities of platelet-depleted human monocytes.

The significant numbers of platelet contaminants bound to the surface of freshly isolated human monocytes can be removed during incubations in fresh human serum. We used cells purified by these means to examine the cyclooxygenase and lipoxygenase metabolites of arachidonic acid synthesized in response to various stimuli. Thromboxane is the single major product synthesized by human monocytes in response to inflammatory particles (opsonized zymosan or immunoglobulin G complex-coated beads). The molar amounts produced were equivalent to those by platelets stimulated with thrombin. In contrast, exposure to calcium ionophore A23187 led to greatly enhanced lipoxygenase metabolite synthesis. Under these conditions, levels of leukotriene B4 (30 to 70 pmol/10(6) cells) and leukotriene C4 (up to 20 pmol/10(6) cells) production were five- to tenfold higher than those observed with particulate stimuli. The circulating human monocyte is a source of a variety of vasoactive mediators derived from arachidonic acid.

Arachidonate Lipoxygenases↗

Continuous conjunctival and transcutaneous oxygen tension monitoring during resuscitation in a patient.

Conjunctival (PcjO2) and transcutaneous (PtcO2) oxygen tensions were serially measured in a patient with multiple stab wounds. Even though blood pressure was normal, severe hypovolemia due to hemorrhage was detected in the emergency department by abnormally low PcjO2/PaO2 and PtcO2/PaO2 ratios. The adequacy of resuscitation was established by return of these ratios to normal values. The conjunctival sensor stabilized more rapidly than the transcutaneous sensor and is of greater utility in the emergency setting. It was found that conjunctival and transcutaneous oxygen sensors can play an important role in monitoring clinical state and resuscitation of trauma patients.

Adult↗

Continuous monitoring of critically ill patients with transcutaneous oxygen and carbon dioxide and conjunctival oxygen sensors.

Transcutaneous (PtcO2) and conjunctival (PcjO2) oxygen tensions and transcutaneous (PtcCO2) carbon dioxide tension were serially measured in 31 critically ill patients. Sixteen patients maintained a normal or greater blood pressure and 15 patients were severely hypotensive (MAP less than 60 mm Hg) or suffered cardiac arrest while in the emergency department. In hemodynamically stable patients, the correlations between PtcO2 and PaO2, PcjO2 and PaO2, and PtcCO2 and PaCO2 were significant, with correlation coefficients (r values) of 0.62, 0.48, and 0.73, respectively. In hemodynamically unstable patients, there was poor correlation between PtcO2, PcjO2, PtcCO2, and arterial blood gas values. In the severely hypotensive patients, however, PtcO2 and PcjO2 were sensitive real-time monitors of peripheral perfusion and tissue oxygen delivery. Increases in PcjO2 and PtcO2 occurred within three minutes in patients who regained a palpable blood pressure from a pulseless baseline. PtcO2 fell one to five minutes after the loss of blood pressure in patients whose clinical condition deteriorated in the emergency department. Decreases in PcjO2 from previously stable levels occurred over three to four minutes before loss of blood pressure. Transcutaneous and conjunctival sensors can be used as continuous monitors of respiratory status in hemodynamically stable patients. In severely hypotensive patients and during cardiopulmonary resuscitation, these sensors no longer accurately reflect arterial blood gases, but act as sensitive real-time monitors of cardiac function and peripheral perfusion. PcjO2 can detect deterioration of clinical state before alterations in blood pressure occur.

Adult↗

Conjunctival and transcutaneous oxygen monitoring during resuscitation.

Conjunctival (PciO2) and transcutaneous (PtcO2) oxygen tensions were serially measured during cardiopulmonary resuscitation (CPR). Changes in cardiac function and arterial oxygen content were reflected accurately by alterations in PciO2 and PtcO2. PciO2 showed more rapid responses to changes in physiologic state than did PtcO2. Conjunctival and transcutaneous oxygen sensors gave continuous information with respect to oxygen delivery during CPR, and provided real-time assessment of the effectiveness of CPR in terms of peripheral perfusion and tissue oxygenation.

Aged↗

Conjunctival and transcutaneous oxygen monitoring during cardiac arrest and cardiopulmonary resuscitation.

To define the utility of transcutaneous and conjunctival oxygen sensors in the emergency setting, we measured serial conjunctival (PcjO2) and transcutaneous (PtcO2) oxygen tensions during CPR in 11 patients. There was no significant correlation between PaO2 and PtcO2 or PcjO2. Improvement or deterioration in clinical condition as assessed by return or loss of palpable blood pressure was consistently and accurately reflected by PcjO2 and PtcO2. PcjO2 responded to changes in physiologic state more rapidly than did PtcO2, with a reaction time of approximately 60 sec. Conjunctival and transcutaneous oxygen sensors provided continuous information on the effectiveness of CPR in terms of peripheral perfusion and tissue oxygenation, and were a valuable adjunct in monitoring the clinical condition of these critically ill patients.

Conjunctiva↗

Cardiorespiratory responses to fluid administration in peritonitis.

Intravascular volume expansion was studied in 59 critically ill patients with a wide variety of sepsis and in a small group of 12 patients with peritonitis; either 500 ml of 5% albumin solution or 2 units of packed red blood cells were given over a 60-min period. During the 2-h period after volume loading, significant increases in mean arterial pressure (MAP), pulmonary capillary wedge pressure (WP), central venous pressure (CVP), and oxygen consumption (VO2) were observed. One hour after fluid administration MAP had risen from 72 +/- 16 (SD) at baseline to 78 +/- 17 mm Hg (p less than .01), WP from 9 +/- 5 to 16 +/- 7 mm Hg (p less than .05), CVP from 7 +/- 4 to 9 +/- 4 mm Hg (p less than .05) and VO2 from 132 +/- 19 to 148 +/- 31 ml/min X m2 (p less than .01). Improvement in VO2 after volume loading is consistent with the concept that circulatory problems in sepsis result in less VO2 than is needed and that intravascular volume expansion in normovolemic septic patients may improve peripheral perfusion as measured by oxygen uptake.

Adult↗

Detection of blood volume deficits through conjunctival oxygen tension monitoring.

Because acute blood loss may produce abnormal tissue perfusion and oxygenation before affecting blood pressure, we measured conjunctival (PcjO2) and arterial (PaO2) oxygen tensions and blood volume in 16 normotensive emergency department patients whose histories were consistent with significant blood loss. All eight patients with measured blood volume less than 85% of normal, as well as two euvolemic patients, had a PcjO2/PaO2 value of 0.57 or less, yielding a sensitivity of 100%, specificity of 75%, and positive predictive value of 80%. Lowering the cutoff point to 0.50 increased specificity and positive predictive value to 100% while reducing sensitivity to 88%. These results demonstrate that the PcjO2/PaO2 ratio is an early, sensitive, and specific indicator of significant blood volume deficit.

Adolescent↗