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Biomedical subjects

F D Moore

Publications and source records attributed to F D Moore.

At least 73 records · Page 4Linked to original sources
PubMed1988

Recombinant human tumor necrosis factor increases granulocyte cell-surface complement receptor number.

Exposure of human buffy-coat granulocytes to tumor necrosis factor (TNF) produced cellular activation as indicated by an increase in the neutrophil and monocyte cell-surface number of C3b receptors (measured by indirect immunofluorescence). The degree of receptor increase depended on the dose of TNF from 25 to 1250 pg/mL. Results of kinetic analysis confirmed this response: TNF, 250 pg/mL, caused an increase in the C3b receptor number within ten minutes. Purified neutrophils exhibited a similar increase in cell-surface C3b receptors dependent on the concentration of TNF. Tumor necrosis factor could be a mediator of granulocyte activation in patients.

Granulocytes↗
PubMed1988

The effects of complement activation during cardiopulmonary bypass. Attenuation by hypothermia, heparin, and hemodilution.

Complement activation was examined prospectively in 100 cardiopulmonary bypass (CPB) patients. Plasma C3a desArg (C3a) increased (cannulation: 234 +/- 33 ng/mL; 20 minutes on CPB: 622 +/- 51; 2 hours after CPB: 1143 +/- 109, p less than 0.0001). C3a at 2 hours was higher in the 13 patients requiring mechanical ventilation for longer than 1 day (1023 +/- 274) than in the 67 without respiratory complication (568 +/- 45, p less than 0.004). Five more patients were studied for neutrophil activation to confirm that a biologic effect of complement activation occurs during CPB; in these five patients C3a increased to 317% of baseline after 10 minutes on CPB with a corresponding rise in neutrophil cell surface receptors for the complement opsonin C3b (as measured by indirect immunofluorescence) to 168% (p less than 0.05). Both increases were sustained at 30 minutes. Temperature, dilution, and heparin were studied as variables relevant to CPB. Exposure of normal neutrophils to C5a in vitro caused an increase in C3b receptors which was dependent on temperature (0 specific fluorescence at 0 C, 30 at 25 C, 180 at 30 C, and 275 at 37 C). Generation of C3a and C5a in normal serum by zymosan was also temperature-dependent (ng/mL C5a generated: 0.7 at 25 C, 200 at 30 C, and 897 at 37 C; ng/mL C3a generated: 546 at 25 C, 10,872 at 30 C, and 65,667 at 37 C). Serum dilution to 33% decreased ng/mL C5a generated in the same system from 200 to 76 with no effect on C3a. Addition of heparin to 20 U/mL decreased ng/mL C3a generated from 10,872 to 913 and C5a from 200 to 8. Thus, hypothermia, dilution, and heparin protect CPB patients from complement activation by reducing both generation of C3a/C5a and the subsequent cellular response of neutrophil activation.

Cardiopulmonary Bypass↗
PubMed1987

Teaching the two faces of medical history.

In this article, medical history is described as falling into two large classes. The first is macrohistory, the grand sweep of great events over the centuries. The second is microhistory, the small, detailed, historical development of procedures, drugs, and therapies, as well as diagnostic procedures, that provides the basis for today's treatment in medicine, pediatrics, and surgery. Knowledge of both of these aspects of medical history is essential to the safe practice of medicine, as well as to the enjoyable life of the physician or surgeon working in applied biomedical science.

Education, Medical↗
PubMed1987

A single dose of endotoxin activates neutrophils without activating complement.

Both complement (C) and neutrophils (PMN) are activated in critically ill patients. To evaluate the role of endotoxin in this response, we studied C activation products and PMN cell surface receptors in seven normal subjects before and after endotoxin (USRef 20 U/kg) or saline solution administered on separate occasions. By 4 hours, with endotoxin only, all subjects had myalgia, headache, an increase in body temperature and heart rate, and leukocytosis that returned to normal by 24 hours. At the same time, PMN cell surface receptors for the complement opsonin C3b increased, as measured by indirect immunofluorescence, rising to 251 +/- 44% of baseline by 4 hours (p less than 0.01) and remaining elevated at 24 hours (237 +/- 16%, p less than 0.01). PMN receptors for iC3b increased to 308 +/- 49% of baseline by 4 hours (p less than 0.02) and returned to normal by 24 hours. There was no change in plasma of C3a desArg, C4a desArg, and C5a desArg (4 hours: mean C3a: 153.4 +/- 11.5 ng/ml versus 176.2 +/- 16.2 ng/ml for saline solution, p = ns; C4a: 159.6 +/- 32 ng/ml versus 151.4 +/- 21 ng/ml, p = ns; C5a: undetectable). To confirm the lack of C activation, we examined PMN chemotaxis (CTX) to C5a for any impairment caused by prior in vivo exposure to C5a. CTX to C5a was unaffected (4 hours: 109% +/- 22% of normal versus 114% +/- 10% for saline solution, p = ns). PMN CTX to formyl-methionyl-leucine-phenylalanine and PMN phagocytosis and killing of S. aureus were also unaffected by endotoxin. Thus, a single dose of endotoxin produced a subjective febrile illness and precipitated sustained PMN activation as indicated by increased PMN cell surface complement receptor number in the absence of C activation.

Adult↗
PubMed1987

Neutrophil activation after burn injury: contributions of the classic complement pathway and of endotoxin.

We attempt to elucidate the mechanisms of neutrophil (PMN) activation after burn injury. We previously reported prolonged elevations of PMN cell surface complement (C) opsonin receptor levels after burn trauma with a corresponding period of depressed PMN chemotaxis to C5a, which suggests that the C product, C5a, was responsible for PMN activation. However, a lack of direct correlation of C activation with C receptor levels soon after injury raised the possibility of a second PMN-activating substance. We therefore investigated the effect of endotoxin (LPS) on the expression of the C receptors (CR1 and CR3) by normal human PMNs. Concentrations from 0 to 50 ng/ml of LPS 026:B6 caused a dose response increase in the PMN surface expression of CR1 and CR3 as assessed by monoclonal antibody binding and indirect immunofluorescence. The relative CR1-dependent fluorescence rose from a mean of 50 to 385 and CR3 from 50 to 300. Chelation by ethylenediaminetetra acetic acid (EDTA) did not influence this dose response, thus ruling out the possibility of C activation by LPS--an inference supported by the lack of complement activation observed with these concentrations of LPS in normal serum. A similar dose response was obtained in the absence of other cell types or serum, which implies a direct effect that mimicked that of C5a. To determine the mechanism of the later, prolonged C activation after burn injury, we next examined C activation products in 22 patients with burn injuries. Elevations of plasma C3a desArg were present and persisted for 50 days. Elevations were at maximum levels on days 9 through 13 postburn (mean +/- standard error of mean [SEM], 496 +/- 47 ng/ml versus normal 113 +/- 32; p less than 0.01). These were accompanied by elevations of C4a desArg (917 +/- 154 ng/ml versus normal 424 +/- 50; p less than 0.01), which are indicative of classic pathway activation. Finally, we examined PMN function, phagocytosis and percentage killing of Staphylococcus aureus, and found PMN function to be unaltered in the 22 patients. Thus PMN activation after burn injury appears to be caused by LPS soon after injury and by C5a later after injury and affects only selected PMN functions.

Adolescent↗
PubMed1986

Neutrophil activation in thermal injury as assessed by increased expression of complement receptors.

We studied neutrophil activation in patients with burns by serial immunofluorescent measurement of neutrophil expression of the complement opsonin receptors CR1 and CR3. CR1-dependent fluorescence was initially (days 0 through 5 after the burn) elevated (mean +/- SEM, 294 +/- 42 vs. 63 +/- 6 in the controls; P less than 0.001) and gradually returned to normal (days 6 through 8, 270 +/- 62, P less than 0.001; days 9 through 13, 185 +/- 38, P less than 0.001; days 14 through 19, 143 +/- 27, P less than 0.001; and days 20 through 50, 93 +/- 5, P less than 0.04). CR3-dependent fluorescence paralleled that of CR1. Neutrophil chemotaxis in response to zymosan-activated serum, a source of C5a, was depressed (days 0 through 5, 77 +/- 4 percent of control, P less than 0.001; days 6 through 8, 70 +/- 4 percent, P less than 0.001; days 9 through 13, 74 +/- 3 percent, P less than 0.001; days 14 through 19, 90 +/- 4 percent, P less than 0.01; and days 20 through 50, 97 +/- 3 percent, P not significant) and inversely correlated with CR1- and CR3-dependent fluorescence (r = -0.559, P less than 0.001; and r = -0.709, P less than 0.001, respectively). Plasma C3a desArg levels were above normal (100 +/- 5 ng per milliliter) throughout (days 0 through 5, 305 +/- 42; days 6 through 8, 546 +/- 69; days 9 through 13, 490 +/- 72; days 14 through 19, 409 +/- 54; and days 20 through 50, 260 +/- 36; all P less than 0.005). Thus, neutrophils in burned patients were activated as indicated by increased expression of complement receptors. The correlation between this increase and the depression of chemotaxis in response to zymosan-activated serum suggests that C5a is responsible for systemic neutrophil activation, which may contribute to the increased susceptibility to infection of patients with burns.

Adult↗
PubMed1986

Abdominal pain in neutropenic cancer patients.

A review of 58 patients with malignancies (age range, 14-73 years), who required surgical consultation for acute abdominal pain in the setting of neutropenia (granulocyte count less than 1000/mm3) after chemotherapy was conducted. Ninety percent had fevers greater than 37.8 degrees C, 30% had diarrhea or melena, and 25% had diminished bowel sounds. Five of the 29 patients (17%) with localized pain had surgical intervention; 3 of 29 patients (10%) with generalized pain underwent operations (2 for x-ray findings). All eight of these surgically treated patients survived to leave the hospital. Eighteen of the 29 patients with generalized pain were believed to have a similar syndrome of diarrhea (occasionally heme positive) and diffuse abdominal tenderness (some with peritoneal signs and distension), which was termed "neutropenic enteropathy." Eleven of these 18 patients had their symptoms resolve with antibiotic therapy, aggressive fluid replacement, and a return of their granulocyte count to normal. The other seven died of pneumonia (two), unknown causes (one), and diffuse enterocolitis throughout the intestinal tract (four documented at autopsy). The overall 30-day mortality rate in this series was 34%. Several factors correlated significantly with mortality: hypotension at the onset of pain (80% mortality), bacteremia (63% mortality), and fungemia (100% mortality). Absolute leukocyte count and absolute platelet count did not correlate with mortality. This study reaffirms that patients with neutropenic enteropathy are best treated conservatively. Patients with surgically correctable disease were identified by specific focal findings on examination or x-ray.

Abdomen↗
PubMed1985

Surgical streams in the flow of health care financing. The role of surgery in national expenditures: what costs are controllable?

The dollar flow in United States medical care has been analyzed in terms of a six-level model; this model and the gross 1981 flow data are set forth. Of the estimated $310 billion expended in 1981, it is estimated that $85-$95 billion was the "surgical stream", i.e., that amount expended to take care of surgical patients at a variety of institutional types and including ambulatory care and surgeons' fees. Some of the determinants of surgical flow are reviewed as well as controllable costs and case mix pressures. Surgical complications, when severe, increase routine operative costs by a factor of 8 to 20. Maintenance of high quality in American surgery, despite new manpower pressures, is the single most important factor in cost containment. By voluntary or imposed controls on fees, malpractice premiums, case mix selection, and hospital utilization, a saving of $2.0-$4.0 billion can be seen as reachable and practical. This is five per cent of the surgical stream and is a part of the realistic "achievable" savings of total flow estimated to be about +15 billion or 5 per cent.

Cost Control↗