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Biomedical subjects

J A Mannick

Publications and source records attributed to J A Mannick.

At least 91 records · Page 5Linked to original sources

Observations on the use of thrombolytic agents for thrombotic occlusion of infrainguinal vein grafts.

Vein graft failure remains a major challenge for the vascular surgeon. Thrombolysis of occluded vein grafts has shown promising short-term results in restoring vein graft patency, however, the long-term results are not established. This study examines the long-term patency and limb salvage after successful thrombolysis and revision of 22 thrombosed vein grafts in 21 patients. There were 17 men and four women with an average age of 60 years (38 to 77 years). Failed vein grafts had an average primary patency of 19 months (1 to 84 months) and included eight in situ grafts and 14 non-in situ grafts. Twelve grafts were to the popliteal level, whereas 10 were infrapopliteal. Thrombolytic agents used included urokinase (15), tissue plasminogen activator (5), and streptokinase (2). After successful thrombolysis, 19 grafts underwent 26 additional procedures including percutaneous transluminal angioplasty (9), vein patch angioplasty (4), vein interposition or jump extension graft (9), or other procedures (4). Three patients had no additional procedure, but one was placed on sodium warfarin (Coumadin). After successful initial vein graft salvage, life-table analysis revealed a 36.6% +/- 11.9% patency at 1 year and a 22.9% +/- 11.6% patency at 3 years. After secondary failure six patients had further interventions contributing to an improved limb salvage of 66.9% +/- 11.6% at 1 year and 60.3% +/- 19.0% at 3 years. The results suggest that thrombosed vein grafts initially salvaged with thrombolysis and revision do not have a favorable long-term patency, and that a premium must be placed on the detection of the failing vein graft before thrombosis.

Adult↗

Screening for hypercoagulable states in vascular surgical practice: a preliminary study.

The prevalence and importance of hypercoagulable states in the general vascular surgical population is unknown. Antithrombin III, protein C, protein S, plasminogen, lupus-like anticoagulant, and heparin-induced platelet activation were determined prospectively in 158 patients with aneurysmal (27), renovascular (1), cerebrovascular (28), aortoiliac (31), or infrainguinal (71) disease. Sixteen abnormal test results were obtained in 15 patients (9.5%) as follows: deficiencies of antithrombin III (2), protein C (4), and protein S (1) and presence of lupus-like anticoagulant activity (5) and heparin-induced platelet activation (4). Reconstructive surgery was performed in 137 of the study patients. Five reconstructions, all infrainguinal bypass grafts, suffered thrombosis within 30 days. Early graft thrombosis occurred in three (27%) of 14 patients with abnormal preoperative test results compared to two (1.6%) of 123 patients with normal testing (p less than 0.01). Of the three patients with abnormal test results and graft thrombosis, lupus-like anticoagulant was detected in two and heparin-induced platelet activation in one. This preliminary study supports routine preoperative screening for lupus-like anticoagulant and heparin-induced platelet activation in patients undergoing infrainguinal reconstruction. Hypercoagulable states appear to be sufficiently common and important in the general vascular surgical population to warrant further investigation.

Adult↗

Circulating human peripheral blood granulocytes synthesize and secrete tumor necrosis factor alpha.

Circulating peripheral blood polymorphonuclear neutrophils (PMNs) have long been considered terminally differentiated cells that do not synthesize or secrete protein. However, work of others and ourselves has shown that PMNs can secrete the cytokine interleukin 1. In the present study we investigated whether circulating PMNs are capable of synthesizing and secreting another cytokine, tumor necrosis factor alpha (TNF-alpha). Highly purified (greater than 99% granulocytes) PMNs were isolated from normal human volunteer blood and cultured with or without bacterial lipopolysaccharide (LPS) for up to 24 hr. Cell culture supernatants were collected and tested for TNF-alpha, and total RNA was isolated from cells at various times after stimulation and assessed for TNF-alpha mRNA by Northern blot techniques. The results showed that message for TNF-alpha was produced after 60 min of in vitro stimulation with LPS and was maximal at about 4 hr. TNF-alpha was secreted into the supernatant of unstimulated PMNs from two different donors during 24 hr of culture (35-50 pg/ml), but significantly more (160-190 pg/ml) was secreted by PMNs when stimulated with LPS. PMNs from six other normal volunteers showed significant LPS-stimulated secretion of TNF at 60-180 min of culture. The secreted product also had biological activity against the TNF-sensitive L-M cell line, confirming that PMNs can make and secrete immunologically and biologically active TNF. Since it is also possible for monocytes to synthesize and secrete TNF, the amount of TNF secreted by a monocyte population equal to 20% of the PMNs cultured was measured. The results showed that monocytes at a concentration 20 times that potentially contaminating the PMN populations cultured could not produce as much TNF (unstimulated, 26-65 pg/ml; stimulated, 32-87 pg/ml). The PMN must now be considered a cell capable of altering the acute inflammatory response and modulating the immune response through the synthesis and release of cytokines.

Cell Line↗

Selective evaluation and management of coronary artery disease in patients undergoing repair of abdominal aortic aneurysms. A 16-year experience.

Reduction of cardiac mortality associated with abdominal aortic aneurysm (AAA) repair remains an important goal. Five hundred consecutive urgent or elective operations for infrarenal nonruptured AAA were reviewed. Patients were divided into three groups based on preoperative cardiac status: group I (n = 260, 52%), no clinical or electrocardiographic (ECG) evidence of coronary artery disease (CAD); group II (n = 212, 42.2%), clinical or ECG evidence of CAD considered stable after further evaluation with studies such as dipyridamole-thallium scanning, echocardiography, or coronary arteriography; group III (n = 28, 5.6%), clinical or ECG evidence of CAD considered unstable after further evaluation. Group I had no further cardiac evaluation and groups I and II underwent AAA repair without invasive treatment of CAD. Group III underwent repair of cardiac disease before (n = 21) or coincident with (n = 7) AAA repair. In all instances, perioperative fluid volume management was based on left ventricular performance curves constructed before operation. The 30-day operative mortality rate for AAA repair in all 500 patients was 1.6% (n = 8). There was one (0.4%) cardiac-related operative death in group I, which was significantly less than the five (2.4%) in group II (p less than 0.02). Total mortality for the two groups were also significantly different, with one group I death (0.4%) and seven group II deaths (3.3%), (p less than 0.02). These data support the conclusions that (1) the leading cause of perioperative mortality in AAA repair is myocardial infarction, (2) correction of severe or unstable CAD before or coincident with AAA repair is effective in preventing operative mortality, (3) patients with known CAD should be investigated more thoroughly to identify those likely to develop perioperative myocardial ischemia so that their CAD can be corrected before AAA repair, and (4) patients with no clinical or ECG evidence of CAD rarely die of perioperative myocardial infarction, and thus selective evaluation of CAD based on clinical grounds in AAA patients is justified.

Aorta, Abdominal↗

Early detection of saphenous vein arterial bypass graft stenosis by color-assisted duplex sonography: a prospective study.

We propose a simple and rapid technique for the postoperative surveillance of developing stenosis in lower extremity saphenous vein arterial bypass grafts that uses color-assisted duplex sonography. Color Doppler flow images are used to identify points of altered flow dynamics. These points are subsequently analyzed by duplex sonography, with doubling of the peak systolic velocity at the point of suspected stenosis considered the diagnostic threshold for significant stenosis. A segment-by-segment comparison made with arteriography in 14 patients (15 grafts, 92 segments) showed this approach to be 95% sensitive (18/19) and 100% specific (73/73) for the detection and localization of focal graft stenoses that involve greater than 50% narrowing of the lumen diameter. We conclude that color-assisted duplex sonography can accurately detect the presence of saphenous vein arterial bypass graft stenoses.

Aged↗

Determination of the extent of lower-extremity peripheral arterial disease with color-assisted duplex sonography: comparison with angiography.

Color-assisted duplex sonography combines color Doppler flow imaging with duplex sonography to rapidly survey the vasculature. Color Doppler sonography displays the motion of flowing blood on a sonogram and is used to visualize directly arterial lumen narrowing of greater than 50%. Absence of Doppler signals signifies arterial occlusion. Preangiographic triage of patients for surgical or interventional therapy requires that a rapid and accurate survey be performed of the extent of arterial disease. Color-assisted duplex sonography was applied prospectively in 17 consecutive patients with the clinical diagnosis of peripheral arterial disease who had not previously undergone angiography. Results of angiography of the femoropopliteal arteries were graded and localized in one of seven approximately equal arterial segments. These were compared with similar segmental maps made with sonography. For the detection of stenosis or occlusion in any of the 238 segments, the sensitivity was 0.88 (49/56), specificity 0.95 (173/182), and accuracy 0.93 (222/238). The average time taken to survey both limbs was 29 min. We conclude that color-assisted duplex sonography is an accurate and rapid tool for the noninvasive mapping of the extent of femoropopliteal arterial disease.

Adult↗

Reperfusion pulmonary edema.

Reperfusion following lower-torso ischemia in humans leads to respiratory failure manifest by pulmonary hypertension, hypoxemia, and noncardiogenic pulmonary edema. The mechanism of injury has been studied in the sheep lung lymph preparation, where it has been demonstrated that the reperfusion resulting in pulmonary edema is due to an increase in microvascular permeability of the lung to protein. This respiratory failure caused by reperfusion appears to be an inflammatory reaction associated with intravascular release of the chemoattractants leukotriene B4 and thromboxane. Histological studies of the lung in experimental animals revealed significant accumulation of neutrophils but not platelets in alveolar capillaries. We conclude that thromboxane generated and released from the ischemic tissue is responsible for the transient pulmonary hypertension. Second, it is likely that the chemoattractants are responsible for leukosequestration, and, third, neutrophils, oxygen-derived free radicals, and thromboxane moderate the altered lung permeability.

Animals↗

Immunomodulatory effects of systemic low-dose recombinant interleukin-2 and lymphokine-activated killer cells in humans.

The adoptive immunotherapy of human cancer using lymphokine-activated killer (LAK) cells in combination with high-dose systemic recombinant interleukin-2 (rIL-2) has been associated with global changes in several hematological and immunological parameters while imposing profound toxicity on patients. We have evaluated an alternative LAK cell therapy utilizing low-dose systemic rIL-2 is also characterized by significant changes in immunological and hematological parameters, which are qualitatively similar to those induced by high-dose rIL-2. Low-dose systemic rIL-2, given by i.v. bolus, is cleared to baseline levels within 240 min of administration. The induction of lymphocytosis and eosinophilia, which has characterized other protocols, is also a feature of this protocol. In addition, low-dose systemic rIL-2/LAK cell immunotherapy results in increased peripheral blood mononuclear cell (PBMC) expression of T-cell activation markers such as OKIa, OKT10 and IL-2 receptor. PBMC sampled approximately 100 h after the final infusion of LAK cells demonstrated a statistically significant increase in their ability to kill natural killer (NK)-sensitive and NK-resistant cell lines such as K562 and Daudi compared to baseline values (P less than .05). These data suggest that rIL-2-based immunotherapy using low-dose rIL-2 is capable of inducing quantitative hematological and immunological changes while (in combination with LAK cells) retaining the ability to mediate tumor regression in vivo.

Adjuvants, Immunologic↗

What is the proper role of polytetrafluoroethylene grafts in infrainguinal reconstruction?

Polytetrafluoroethylene grafts have been used extensively for infrainguinal vascular reconstruction either as the conduit of choice or as a substitute when saphenous vein is unavailable. Although numerous studies have shown satisfactory early patency rates, the long-term efficacy of these grafts in a large number of patients for specific indications and in various positions has been less well defined. From 1977 to 1987 we used four PTFE grafts from three different manufacturers to perform 300 infrainguinal reconstructions on 240 patients on our vascular service. The indications for surgery were disabling claudication in 28% and limb salvage in 72%. The 30-day operative mortality of 1% was not different from the 1.4% associated with infrainguinal autogenous vein grafting. The 5-year cumulative patency rate achieved with all infrainguinal polytetrafluoroethylene grafts was 35%, significantly higher for grafts placed for claudication (57%) than those placed for limb salvage (24%). There were no significant differences between the above-knee and below-knee locations for distal anastomoses regardless of indication, but femoropopliteal grafts provided significantly higher 5-year patency (37%) than infrapopliteal grafts (12%). Comparison of the 5-year patency rates among the three manufacturers of polytetrafluoroethylene grafts showed no significant differences. Fifty-four polytetrafluoroethylene grafts that failed underwent 67 revisions after catheter thrombectomy or thrombolysis, which resulted in a minimal 11% 5-year patency rate. Based on this experience, it is concluded that infrainguinal polytetrafluoroethylene prostheses provide significantly inferior results when compared with autogenous reconstruction.

Adult↗

Short-term and midterm results of an all-autogenous tissue policy for infrainguinal reconstruction.

Saphenous vein is the optimal conduit for infrainguinal vascular reconstruction. In instances in which this vein is unavailable or of "poor quality," reliance has been placed on a variety of prosthetic materials for bypass grafting. However, long-term patency with these prosthetic grafts has been disappointing. In January 1985 we instituted a policy of using exclusively autogenous tissue for infrainguinal arterial reconstruction. During the ensuing 3-year period, 203 patients underwent 266 arterial operations below the inguinal ligament, with a prosthetic graft used in only 11 instances (4%). No patient was denied surgery for limb salvage because of a lack of available autogenous vein. Thirty-three percent of procedures were performed for failure of prior revascularization and 73% for limb salvage. The 3-year cumulative primary patency rate for all autogenous procedures was 72%. Procedures were divided into those that used greater saphenous vein (patency 77%) vs autogenous alternatives such as bypass with arm vein or lesser saphenous vein, vein patch angioplasty, and endarterectomy (patency 64%). The operative mortality rate was 1.4% and the 3-year limb salvage rate was 89%. Autogenous infrainguinal reconstruction can be performed in almost every instance with acceptable results, suggesting that the need for prosthetic bypass grafts in the lower extremity is less than has been previously reported.

Adult↗

Salvage of occluded arterial bypass grafts by means of thrombolysis.

Seventy-two thrombosed peripheral arterial bypass grafts in 62 patients were treated by local intraarterial thrombolytic infusion. The initial success rate was 69% (50 of 72 grafts). Graft material and location had no significant effect on the initial results. Urokinase was used in 43 cases with a 84% success rate, and streptokinase was used in 29 cases with a 48% success rate. After a follow-up period that ranged from 2 to 58 months, 27 grafts remained patent, with an average patency duration of 15 months (median 8 months). Overall graft patency at the end of 1 year was 60% applying life-table analysis. Factors that were evaluated to determine their effect on long-term patency included graft age and material, graft location, and the presence or absence of an underlying correctable lesion. The most significant factor in long-term patency was the presence of a lesion that was correctable by surgical revision or balloon angioplasty. In 25 grafts with underlying stenotic lesions, the 1-year patency was 86% after successful treatment. Twenty-five grafts without detectable lesions had 37% 1-year patency.

Adult↗

Noncardiogenic pulmonary edema after abdominal aortic aneurysm surgery.

Limb ischemia in experimental animals leads to white blood cell (WBC) and thromboxane (Tx)A2 dependent pulmonary dysfunction. This study examines the pulmonary sequelae of lower torso ischemia in 20 consecutive patients aged 63 +/- 5 years (mean +/- SEM) who underwent elective abdominal aortic aneurysm surgery. After 30 minutes of aortic cross-clamping, plasma TxB2 levels had risen from 77 +/- 26 pg/ml to 359 +/- 165 pg/ml (p less than 0.01) and was temporally related to increases in mean pulmonary artery pressure (MPAP) from 18 +/- 1 to 23 +/- 3 mmHg (p less than 0.01), as well as to increases in pulmonary vascular resistance (PVR) from 0.07 +/- 0.02 to 0.12 +/- 0.02 mmHg sec/ml (p less than 0.01). Each time that the aortic clamp was repositioned and with final declamping, after 83 +/- 10 minutes, there were further increases in MPAP to a peak of 32 +/- 2 mmHg (p less than 0.01) and in PVR to 0.26 +/- 0.030 mmHg sec/ml (p less than 0.01), corresponding to a plasma TxB2 level of 406 +/- 177 pg/ml (p less than 0.01). MPAP and PVR returned to baseline values within 30 minutes of declamping. Ten minutes after removal of the aortic clamp, platelet levels had fallen from 180 +/- 41 to 97 +/- 17 X 10(3)/mm3 (p less than 0.01) and WBC levels from 8900 +/- 1100 to 4700 +/- 400/mm3 (p less than 0.01). Both platelets and WBC returned towards normal levels, but at 24 hours, while WBC was elevated at 13000 +/- 900/mm3 (p less than 0.01), platelets were 44% of baseline at 135 +/- 14 X 10(3)/mm3 (p less than 0.01). Four to 8 hours after surgery, pulmonary dysfunction was manifest by increases in physiologic shunt from 9 +/- 2% to 16 +/- 2% (p less than 0.01), and peak inspiratory pressure (PIP) from 23 +/- 2 to 33 +/- 2 cmH2O (p less than 0.01). Chest radiography demonstrated interstitial pulmonary edema in all patients, whereas pulmonary artery wedge pressure was 12 +/- 2 mmHg, excluding the possibility of left ventricular failure. After 24 hours, pulmonary edema had resolved, and the PIP and PaO2 had both returned to baseline. These data indicate that reperfusion of the ischemic lower torso leads to the synthesis of TxA2, an event temporally related to pulmonary hypertension and transient leukopenia with subsequent pulmonary microvascular injury manifest by interstitial edema.

Aged↗

Pulsatile masses surrounding vascular prostheses: real-time US color flow imaging.

A prospective evaluation of color flow mapping and real-time ultrasound was performed to determine if pseudoaneurysms could be distinguished from other causes of masses surrounding vascular grafts of the lower extremities. Twelve palpable pulsatile masses were imaged. Diagnoses were confirmed at angiography (n = 11), computed tomography (n = 7), aspiration biopsy (n = 5), and operative intervention (n = 6). A swirling pattern of blood flow was seen in six of seven cases of pseudoaneurysm. Lack of flow signals was noted in four of the five collections representing hematoma (n = 2) or infection (n = 2). The seventh case was later shown to be an infected, thrombosed pseudoaneurysm. The single false-positive diagnosis was made early in the series when the flow signals detected were due to transmitted arterial pulsations. The authors conclude that color Doppler flow imaging is useful in the differential diagnosis of pulsatile masses associated with prosthetic grafts. Prosthetic graft pseudoaneurysms have a specific appearance of swirling blood flow arising from a wide neck and are distinguishable from traumatic or iatrogenic pseudoaneurysms of the native vascular tree.

Aged↗

Pulmonary edema after aneurysm surgery is modified by mannitol.

Abdominal aortic aneurysmectomy (AAA) results in thromboxane (Tx)A2 generation, a rise in mean pulmonary artery pressure (MPAP), leukopenia, and noncardiogenic pulmonary edema. This study tests whether mannitol, a hydroxyl radical scavenger, modifies these events. Patients received mannitol 0.2 g/kg (n = 14) or saline (n = 12) intravenously before infrarenal aortic clamping. With saline, 30 minutes after clamping, plasma TxB2 levels rose from 124 to 290 pg/mL (p less than 0.01), and MPAP rose from 19 to 27 mmHg (p less than 0.01). Aortic clamp release led to further increases in plasma TxB2 to 378 pg/mL (p less than 0.01) and MPAP to 34 mmHg (p less than 0.01). The white blood count (WBC) fell from 9800 to 4400/mm3 (p less than 0.01). Four to eight hours after surgery, physiologic shunting (Q[sc]S[xsc]/Q[sc]T[xsc]) rose from 9% to 20% (p less than 0.01) and peak inspiratory pressure (PIP) increased from 22 to 32 cmH2O (p less than 0.01). Chest radiography demonstrated pulmonary edema while the pulmonary wedge pressure was 12 mmHg, excluding left ventricular failure. By 24 hours pulmonary edema resolved and the PIP and PaO2 returned to baseline. Mannitol treatment relative to saline, during and after aortic clamping reduced plasma TxB2 levels to 155 and 198 pg/mL, respectively (p less than 0.01); MPAP to 21 and 26 mmHg (p less than 0.01); minimized the decline in WBC to 5850/mm3 (p less than 0.01), and the postoperative rise in Q[sc]S[xsc]/Q[sc]T[xsc] to 12%, and PIP to 28 cmH2O (both p less than 0.01). Chest radiography showed no pulmonary edema. Finally in vitro studies documented that mannitol 1 to 10(-4)M, but not dextrose, in a dose-dependent manner inhibited Tx synthesis by ADP-activated platelets. These data indicate that mannitol maintains pulmonary function after AAA by limiting ischemia-induced thromboxane synthesis.

Aged↗

Femoropopliteal reconstruction for claudication. The risk to life and limb.

The current study was undertaken to examine the results of femoropopliteal bypass grafting with intermittent claudication as the indication. Of 1173 infrainguinal reconstructions carried out on our service during the past decade, 249 (21%) consecutive femoropopliteal grafts were performed for disabling claudication in 191 patients. The primary five-year cumulative patency rates were 78% for autogenous vein and 52% for polytetrafluoroethylene grafts. There were two (0.8%) 30-day operative deaths and a subsequent five-year amputation rate of 2.4% for both groups. Femoropopliteal reconstruction for claudication may therefore be carried out with acceptably low operative mortality and a subsequent amputation rate comparable with that anticipated from the natural history of the disease. While the five-year patency rate is significantly higher utilizing autogenous vein grafts, symptomatic relief may be expected with prosthetic grafts in approximately half the patients without incurring a higher risk of limb loss.

Adult↗

Management of ruptured or symptomatic abdominal aortic aneurysms.

During the past 15 years, the operative mortality for elective repair of abdominal aortic aneurysms has declined; this favorable trend has very likely resulted from simplified operative technique and improved perioperative management. Unfortunately, however, there has been no comparable decline in the mortality associated with repair of ruptured abdominal aortic aneurysms. The management of these patients remains a challenge to even the most skilled and experienced vascular surgeon.

Abdomen, Acute↗

Recombinant interleukin-2 (rIL-2) improves immune response and host resistance to septic challenge in thermally injured mice.

Impaired immune competence leading to decreased resistance to sepsis is a major cause of death in burn patients. We have previously shown that increased mortality from a septic challenge correlated with impaired splenocyte interleukin-2 (IL-2) production and response to T cell mitogens in mice subjected to a 25% surface area scald burn. We report now that the addition of recombinant (r) IL-2 (100 U/ml) in vitro to splenocytes from burned animals restored mitogen responses to normal. Burned mice intraperitoneally received 16,000 U of rIL-2 (selected on the basis of dose-response experiments) once daily in 0.5 ml 5% dextrose (5% D) on days 1 through 6 after thermal injury and were compared with burned mice treated with only 5% D. Both groups were subjected to cecal ligation and puncture 10 days after burn; 4 days later, there were no survivors in the 5% D group, whereas 45% of the rIL-2 group remained alive (p = 0.001; Gehan statistic). We found that rIL-2 treatment at the dose selected resulted in no apparent toxicity in burned mice. Finally, splenocytes from rIL-2-treated burned mice showed improved responses to T cell mitogens in vitro compared with 5% D-treated controls. We conclude that rIL-2 therapy may have a role in the restoration of immune competence after thermal injury.

Animals↗