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Biomedical subjects

J A Mannick

Publications and source records attributed to J A Mannick.

At least 109 records · Page 6Linked to original sources
PubMed1988

Temporal correlation of impaired immune response after thermal injury with susceptibility to infection in a murine model.

Suppression of cellular immunity and increased susceptibility to sepsis frequently accompany thermal injury. However, a convincing association between the two has been difficult to establish in human beings. Therefore we chose to investigate the relationship of impaired cell-mediated immunity with susceptibility to sepsis in an animal model. We studied the response to phytohemagglutinin (PHA) and interleukin-2 (IL-2) production by splenocytes from mice subjected to a standard 25% scald burn and killed at intervals of 3, 5, 7, 10, 14, and 25 days after thermal injury. Burned mice were compared in all instances to sham-burn animals (i.e., animals that had been anesthetized and shaved but not burned). We also studied mortality after cecal ligation and puncture (CLP), as a septic challenge, in burned and control animals at the same postburn intervals. We found maximal suppression (50% to 55%) of the PHA response at 10 to 14 days after injury and maximum suppression (68%) of IL-2 production at 7 days. Both of these parameters returned to normal by postinjury day 28. Mortality after CLP increased gradually from control levels after thermal injury up to a maximum of 88% on postburn day 10 and also returned to control levels after 28 days after burn. Significant correlations were found between mortality after CLP in the postburn period and suppression of the PHA response, on the one hand, and the suppression of IL-2 production, on the other (r = 0.89 and 0.91, respectively; p less than 0.05). This result implies a causal relationship between impaired cell-mediated immunity and susceptibility to sepsis after burn injury.

Animals↗
PubMed1987

Suppression of interleukin 2 production in an animal model of thermal injury is related to prostaglandin synthesis.

We performed studies using an animal model of thermal injury to confirm the observed decrease in interleukin 2 (IL-2) production in burned patients and to explore the underlying mechanisms. Ten mice subjected to a 25% scald were compared with ten anesthetized littermates (controls) and six untreated mice (normal mice) 1, 3, 5, 7, 10, 14, and 21 days after burn. Production of IL-2 by splenocytes was stimulated by concanavalin A alone, or in the presence of the cyclooxygenase inhibitor indomethacin or flurbiprofen. The IL-2 content of the resulting supernatant was determined by the response of the IL-2-dependent cell line CTLL-2. The IL-2 production was significantly suppressed in the burned mice at three days (mean +/- SEM, 30.9% +/- 5.2%), five days (19% +/- 5.5%), seven days (41.6% +/- 6.4%), and 21 days (20% +/- 4.5%). Significant enhancement of IL-2 production by indomethacin was seen in the burned group (mean, 95%), but not in controls (mean, 23.8%) or normal mice (mean, 17.2%), and similar effects were seen with flurbiprofen. In separate experiments the effects of exogenous prostaglandin E2 on lymphocyte blastogenesis and IL-2 production were studied, and an increased susceptibility to the inhibitory effects of prostaglandin E2 was observed following thermal injury.

Animals↗
PubMed1987

Thrombolysis in the treatment of peripheral arterial vascular occlusions.

The efficacy of thrombolytic agents in the management of peripheral arterial disease remains unclear. We reviewed our experience with 64 consecutive episodes of limb-threatening graft or native vessel occlusions. The overall success rate was 59%, with a major complication/mortality rate of 28%. Thrombolytic therapy in patients with occluded vascular grafts required identification of a causative lesion and subsequent adjunctive management with percutaneous transluminal angioplasty or surgery for sustained patency (64%). In contrast, approximately 70% of native vessel occlusions maintained patency whether a causative lesion was identified and corrected or not. Patients who failed thrombolytic therapy had a worse prognosis overall, with 38% undergoing primary amputation, although patients with reconstructable occlusions still had a 64% salvage rate at six months. The review demonstrated that thrombolytic therapy continues to be a useful adjunct in treating the patient with peripheral vascular occlusion, although a significant risk of major complications persists. Patients with graft occlusions successfully treated with thrombolysis require correction of any precipitating lesions for long-term limb salvage, while careful management of patients failing thrombolysis can still achieve significant limb salvage in selected cases.

Aged↗
PubMed1987

Arterial reconstruction at diverse sites using nonreversed autogenous vein. An application of venous valvulotomy.

Improved instrumentation for venous valve extirpation has allowed rapid development of the in situ technique for femoral-tibial arterial reconstruction. Extension of this valvulotomy technique permits the expeditious construction of branched, nonreversed saphenous vein grafts for multiple vessel revascularization, and allows use of veins otherwise unsuitable in length for certain arterial bypass procedures. The nonreversed vein graft also appears to offer advantages over the reversed graft with regard to the size of the proximal and distal anastomoses when used as an aortorenal or iliorenal graft as well as in other anatomic locations. Over the past 30 months these techniques were used to implant 10 vein grafts at diverse sites in nine patients with initial success in all instances and one late graft failure.

Adult↗
PubMed1987

Immature T lymphocytes after injury characterized by morphology and phenotypic markers.

Changes in the peripheral blood mononuclear cell (PBMC) population in patients following both thermal and nonthermal injury were defined by both morphological characteristics and surface phenotype with the monoclonal antibodies T6, OKT9, OKT10, and OKIa1, using a fluorescence activated flow cytometer with gating to separate small cells of the lymphocyte series from larger forms. Lymphocytes with surface antigens that bind T6, OKT9, and OKT10 are rarely found in the peripheral blood of adult patients, except in those with malignancies of the lymphoid system. In both burn and trauma patients the percentage of lymphocytes in the PBMC population after Ficoll-Hypaque separation was significantly reduced as compared with normal controls due to increases in the number of granulocytes, large granular lymphocytes (LGL), and monocytes, often present in immature forms. T6 cells were found in significantly greater numbers in both burn and nonthermal injury patients than in a control group using both small and wide gate settings on the fluorescence-activated flow cytometer. Significant increases in the number of T9+ cells also were observed in both groups for a prolonged period following injury. Significantly increased numbers of the T10+ and Ia1+ cells were detected in burn patients. The response to injury, therefore, involves the appearance in the peripheral blood of immature cells that may express T6, T9, T10, and Ia1 surface antigens. These cells may be present in quantities otherwise seen only in malignant disease.

Adolescent↗
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↗
PubMed1987

A comparison of in situ and reversed saphenous vein grafts for infrainguinal reconstruction.

Despite the recent popularity of the in situ saphenous vein graft for infrainguinal arterial reconstruction, considerable doubt exists as to whether this approach offers any real advantage over conventional reversed vein grafts. Therefore we have reviewed our experience with 675 infrainguinal vein grafts undertaken during the past 10 years. There have been no substantial modifications in the technique used for 535 reversed vein grafts over the 10-year period. During the past 3 years, 140 in situ vein grafts have been carried out with the Leather valvulotome used to incise the venous valves. Life-table analysis of 449 femoropopliteal reversed saphenous vein grafts demonstrated 1- and 3-year cumulative patency rates of 81% and 73%, respectively, and a 5-year patency rate of 63%. Seventy-five femoropopliteal in situ bypasses demonstrated a patency rate of 85% at both 1- and 3-year intervals. Cumulative patency rates for 86 femoroinfrapopliteal reversed saphenous vein grafts were 64% and 62% at 1 and 3 years, respectively. Comparable patency rates for 65 infrapopliteal in situ saphenous vein grafts remained stable at 87% for 3 years. Fifteen of the in situ bypasses were anastomosed to vessels at the ankle or foot level, whereas none of the reversed bypasses was carried that far distally. This experience with both in situ and reversed techniques on one service by the same surgeons demonstrates a clear superiority of the in situ saphenous vein graft for infrapopliteal reconstruction at the 3-year interval.

Actuarial Analysis↗
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

Abnormalities of antibody production after thermal injury. An association with reduced interleukin 2 production.

Antibody (Ab) production was studied in 25 burned patients who were immunized with 0.5 mg of tetanus toxoid adsorbed. Anti-tetanus toxoid (TT) Ab was measured by hemagglutination, radial immunodiffusion, and an enzyme-linked immunosorbent assay, and the results for the patients were compared with those for five similarly immunized healthy controls. As measured by hemagglutination, 12 (63%) of 19 patients had lower Ab responses than all five controls (P less than .05 by chi 2), and the median Ab response during the period of maximum response was significantly less than that in controls (8 vs 15.5 log2 maximum dilution; P = .014). After the initial response, serum Ab levels were not maintained in patients, in contrast to controls. This pattern was demonstrated by all three assays; enzyme-linked immunosorbent assay demonstrated that IgG anti-TT Ab was the major class of Ab produced. In nine patients interleukin 2 production by T lymphocytes was measured simultaneously; it was significantly depressed throughout the study except during the period from 36 to 45 days. The Ab response was also impaired in this patient group. Since maintained antibody production in response to TT is known to be T-cell dependent, these results suggest that inadequate interleukin 2 production leading to reduced T-cell help may be responsible for the lack of a persistent Ab response in these burned patients.

Adolescent↗
PubMed1986

Recognition and management of impending vein-graft failure. Importance for long-term patency.

A previous report from this group indicated a very poor long-term patency rate (19%) for occluded femoro-distal vein grafts that require initial thrombectomy prior to patch angioplasty for documented stenosis. Patients with vein grafts were therefore followed up by Doppler pressure determinations of the ankle/brachial index (ABI) postoperatively at three weeks, six weeks, and every four months thereafter for two years in an effort to identify vein-graft failure prior to actual thrombosis. During the past six years we performed 322 vein grafts of which 29 grafts were identified by diminished Doppler ABI and were found to have stenotic segments on subsequent arteriography. Twenty-two of these patients (group 1) underwent reconstruction with patch angioplasty resulting in a five-year cumulative patency rate of 82%. The remaining seven patients (group 2) underwent percutaneous transluminal angioplasty of their stenotic segments yielding a significantly lower five-year patency rate of 43%. These two groups were compared with a third group fo 25 patients with thrombosed grafts mandating initial thrombectomy prior to patch angioplasty. The thrombectomized group 3 patients demonstrated a significantly lower five-year cumulative patency rate of 28%. These data suggest that patients with femoro-distal bypass vein grafts be followed up at frequent intervals early in their postoperative course with determinations of Doppler ABI measurements. Any significant reduction in Doppler ABI compared with the highest postoperative Doppler determination should be aggressively evaluated with digital-subtraction or routine angiography in an effort to locate a stenotic lesion prior to graft thrombosis. Patients found to have such a graft stenosis are then ultimately treated with patch angioplasty in anticipation of satisfactory long-term patency rates.

Angiography↗
PubMed1986

Suppression of natural killer-cell function in humans following thermal and traumatic injury.

Depressed cell-mediated and humoral immune functions have been reported to occur following severe thermal and traumatic injury. In this study we have questioned whether another immune function, natural killing (NK), is also disturbed in these injured patients. Twenty-two thermally injured patients with burns ranging from 5 to 75% of the total body surface area and 15 traumatically injured patients with injury severity scores ranging from 9 to 56 were followed postinjury and compared to 29 age-matched controls. NK activity was measured as the percentage cytotoxicity in chromium-51 release assays with K562 target cells. The more severely burned patients had significantly depressed NK activity for the 40-day period following injury that remained reduced for the duration of the study. Patients with lesser burns had reduced NK-cell function for the initial 10-day period postburn that returned slowly to the normal range. Traumatically injured patients had depressed NK-cell function during the 3- to 6-day period postinjury. The percentage of cells bearing phenotypic markers for the groups in which NK cells are found was either normal or elevated in these patients. A correlation was found between NK activity and interleukin 2 generation by mononuclear cells from these patients. In order to investigate the mechanism of NK suppression in these patients, NK-cell function was studied following the infusion of cortisol, epinephrine, and glucagon into volunteer subjects in amounts known to reproduce serum levels seen following injury of moderate severity. NK-cell function was reduced an average of 66% following infusion, suggesting that the inhibition of NK-cell function seen in patients may be mediated by the stress response to injury.

Adolescent↗
PubMed1986

Abdominal aortic aneurysm repair in patients with preoperative renal failure.

The purpose of this study was to determine the effect of preoperative renal failure on the outcome of patients undergoing infrarenal abdominal aortic aneurysm (AAA) repair. Of 251 patients undergoing AAA repair from 1977 to 1984, 10% had evidence of preoperative chronic renal failure. These patients were classified according to their preoperative serum creatinine values; group I had preoperative creatinine levels of 2 to 4 mg/dl, group II had creatinine levels greater than 4 mg/dl but no history of hemodialysis, and group III consisted of patients on chronic hemodialysis before operation. One of 16 patients in group I developed transient high-output renal failure postoperatively. Four of the six patients in group II (67%) developed significant postoperative deterioration of renal function and required acute hemodialysis. Of the four patients in group III maintained on chronic hemodialysis preoperatively, one died of sepsis from an ischemic colon. This experience suggests that patients with mild renal dysfunction (serum creatine value less than 4 mg/dl) can undergo elective AAA repair without additional morbidity. Patients on hemodialysis before operation can also safely undergo surgical repair of their AAAs electively if dialyzed the day before operation. Patients with severe renal dysfunction (serum creatinine greater than 4 mg/dl) who are not on hemodialysis should be considered for dialysis preoperatively in an attempt to reduce the high incidence of serious postoperative renal functional deterioration and subsequent morbidity.

Aorta, Abdominal↗
PubMed1986

Disseminated intravascular coagulation caused by abdominal aortic aneurysm.

Disseminated intravascular coagulation (DIC) has been described as an occasional complication of abdominal aortic aneurysm. This is usually a perioperative coagulopathy, which may progress into a hemorrhagic diathesis. Rarely, DIC is present preoperatively as a result of the aneurysm itself. In the presence of additional pathophysiologic factors, a "compensated state" of secondary fibrinolysis may deteriorate into a clinically manifest coagulopathy. Heparin can be a useful adjunct in preoperative management of DIC, but definitive treatment requires surgical repair of the aneurysm. Long-term follow-up is essential to ensure that DIC is due to the aneurysm and that other disease processes are not overlooked. We report a case of DIC caused by an abdominal aortic aneurysm, with resolution after surgical treatment.

Aged↗