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Biomedical subjects

J F McKinsey

Publications and source records attributed to J F McKinsey.

16 recordsLinked to original sources

Therapeutic plasma exchange for the acute management of the catastrophic antiphospholipid syndrome: beta(2)-glycoprotein I antibodies as a marker of response to therapy.

We describe two patients with the catastrophic antiphospholipid syndrome associated with elevation of beta(2)-glycoprotein I antibodies and fulminant thrombotic diatheses. Both patients were treated with therapeutic plasma exchange (TPE), which resulted in a marked decrease in antibody titer accompanied by an improved clinical outcome in one patient (IgG antibody). In the second patient, the outcome was poor despite TPE (IgA antibody). There were no significant complications of TPE in either case. Because of the fulminant nature of the catastrophic antiphospholipid syndrome, we conclude that a trial of TPE is warranted for the acute management. Further studies are needed to clarify which patients may benefit from this treatment.

Amputation, Surgical

Assessing outcomes, costs, and benefits of emerging technology for minimally invasive saphenous vein in situ distal arterial bypasses.

BACKGROUND: Instrumentation for a minimally invasive angioscopic in situ peripheral arterial bypass (MIAB) with catheter-directed side-branch occlusion has recently been approved for use. Despite the attractiveness of this approach (2 short incisions), benefits such as lower morbidity and shorter hospitalizations remain undocumented. To justify wide acceptance, minimally invasive surgical techniques must match conventional procedures in durability and cost while enhancing patient comfort. Often such comparisons are difficult during the implementation phase of a new procedure. OBJECTIVE: To compare the outcomes of the MIAB procedures with a concurrent group of patients undergoing conventional in situ bypass procedures. DESIGN: Retrospective review. SETTING: University medical center. PATIENT: The first 20 consecutive MIAB procedures in 19 patients performed between August 1, 1995, and July 31, 1997, were compared with 19 contemporaneous consecutive conventional in situ bypass procedures performed at the same institution. MAIN OUTCOME MEASURES: Operative time, postoperative length of stay, hospital costs, complications, primary assisted and secondary patency, limb salvage, and survival. RESULTS: The patient groups were comparable with respect to age, sex, incidence of smoking, coronary artery disease, hypertension, diabetes, renal failure, cerebrovascular disease, indication, and distal anastomosis level. The median operative time was significantly greater for the MIAB group (6.6 hours vs 5.7 hours; P=.009), and intraoperative completion arteriography more frequently showed retained arteriovenous fistulas in the MIAB group (55% vs 21%; P=.05). The median postoperative length of stay and total cost were 6.5 days and $18,000 for the MIAB group and 8 days and $27,800 for the conventional group (P > or = .05). There were no significant differences in major complications (10% in the MIAB group vs 11% in the conventional group), wound complications (10% vs 11%, respectively), primary assisted patency at 1 year (68%+/-11% vs 78%+/-10%, respectively), secondary patency at 1 year (79%+/-10% vs 88%+/-8%, respectively), limb salvage at 1 year (85%+/-10% vs 94%+/-6%, respectively), or patient survival at 1 year (89%+/-8% vs 61%+/-13%, respectively). CONCLUSION: Patients undergoing the MIAB procedure avoided lengthy vein exposure incisions without sacrificing short-term results. There was a trend toward decreased hospital stay and cost, which may be further realized as the clinical experience broadens. Although longer follow-up and larger cohorts will always be required to define durability, immediate access to outcomes and costs on small numbers of patients facilitates the early assessment of emerging technology.

Adult

Improving perioperative management of carotid endarterectomy.

Multiple components of the perioperative course of patients who undergo carotid endarterectomy must be tightly controlled in order to maintain an acceptably low complication rate. These factors include appropriate patient selection, routine assessment of cardiac risk factors, precise control of blood pressure intraoperatively and postoperatively, meticulous surgical technique and reliable monitoring for intraoperative cerebral ischemia. This discussion focuses on the vascular practice patterns at the University of Chicago and emphasizes intraoperative management and the safe utilization of intraluminal shunts.

Brain Ischemia

Current results of surgical therapy for chronic mesenteric ischemia.

BACKGROUND: Although recognition of chronic mesenteric ischemia has increased in recent years, this disorder has continued to present diagnostic and therapeutic challenges. OBJECTIVE: To examine the modern results of surgical revascularization for chronic mesenteric ischemia. DESIGN: Retrospective review. SETTING: University medical center. PATIENTS: The management of 24 consecutive patients (mean +/- SEM age, 58 +/- 3 years; 5 men, 19 women) who were undergoing surgical treatment of chronic mesenteric ischemia between 1986 and 1996 was reviewed. INTERVENTION: Surgical mesenteric revascularization. MAIN OUTCOME MEASURES: Postoperative course, long-term graft patency rate, and long-term symptom-free survival rate. RESULTS: The most frequent presenting symptoms were postprandial abdominal pain (18 patients [75%]) and weight loss (14 patients [58%]). Less specific complaints included nausea and vomiting (8 patients [33%]), diarrhea (7 patients [29%]), and constipation (4 patients [17%]). Atherosclerotic risk factors were common, including tobacco use (20 patients [83%]), coronary artery disease (10 patients [42%]), and hypertension (10 patients [42%]). The cause was identified as atherosclerosis in 21 patients, median arcuate ligament compression in 2 patients who were monozygotic twins, and Takayasu arteritis in 1 patient. Lesions were localized to all 3 major visceral vessels (celiac artery, superior mesenteric artery [SMA], and inferior mesenteric artery) in 8 patients, celiac artery and SMA in 13, SMA alone in 2, and SMA and inferior mesenteric artery in 1. Seventeen patients underwent antegrade reconstructions from the supraceliac aorta to the SMA and/or celiac artery; 7 patients underwent revascularization by use of a retrograde bypass that originated from the infrarenal aorta or a prosthetic graft. There were no perioperative deaths although 1 patient died in the hospital 6 weeks after early graft failure and sepsis (overall in-hospital mortality, 4%). Follow-up ranged from 3 months to 10 years (median, 2.4 years). The mean +/- SEM 5-year primary graft patency rate, as objectively documented by use of contrast angiography or duplex scanning in 19 of 24 patients, was 78% +/- 11%. Primary failure was documented in 3 patients (at 3 weeks, 5 months, and 7 months). Two patients required a thrombectomy; 1 of these patients subsequently died of an intestinal infarction. The mean +/- SEM 5-year survival rate by use of life-table analysis was 71% +/- 11%. No patient with a patent graft experienced a symptomatic recurrence. CONCLUSIONS: Chronic mesenteric ischemia is usually a manifestation of advanced systemic atherosclerosis. Symptoms almost always reflect midgut ischemia in the distribution of the SMA. An antegrade bypass from the supraceliac aorta can be performed with acceptable operative morbidity and is currently the preferred reconstructive technique. Surgical revascularization affords long-term symptom-free survival in a majority of patients with chronic mesenteric ischemia.

Adult

Acute mesenteric ischemia.

The morbidity and mortality of acute mesenteric ischemia have remained high over the past 30 years despite heightened sensitivity to the diagnosis. Because the duration of the ischemic episode is the most significant determinant of outcome, an aggressive diagnostic and treatment protocol must be maintained. Although this stance may precipitate a number of negative angiographic studies, such an approach is the only opportunity for salvage in these critically ill patients.

Acute Disease

Juxtalumenal location of plaque necrosis and neoformation in symptomatic carotid stenosis.

PURPOSE: The structural features that underlie carotid plaque disruption and symptoms are largely unknown. We have previously shown that the chemical composition and structural complexity of critical carotid stenoses are related to plaque size regardless of symptoms. To further determine whether the spatial distribution of individual plaque components in relation to the lumen corresponds to symptomatic outcome, we evaluated 99 carotid endarterectomy plaques. METHODS: Indications for operation were symptomatic disease in 59 instances (including hemispheric transient ischemic attack in 29, stroke in 19, and amaurosis fugax in 11) and angiographic asymptomatic stenosis > 75% in 40. Plaques removed after remote symptoms beyond 6 months were excluded. Histologic sections from the most stenotic region of the plaque were examined using computer-assisted morphometric analysis. The percent area of plaque cross-section occupied by necrotic lipid core with or without associated plaque hematoma, by calcification, as well as the distance from the lumen or fibrous cap of each of these features, were determined. The presence of foam cells, macrophages, and inflammatory cell collections within, on, or just beneath the fibrous cap was taken as an additional indication of plaque neoformation. RESULTS: The mean percent angiographic stenosis was 82% +/- 11% and 79% +/- 13% for the asymptomatic and symptomatic groups, respectively (p > 0.05). The necrotic core was twice as close to the lumen in symptomatic plaques when compared with asymptomatic plaques (0.27 +/- 0.3 mm vs 0.5 +/- 0.5 mm; p < 0.01). The percent area of necrotic core or calcification was similar for both groups (22% vs 26% and 7% vs 6%, respectively). There was no significant relationship to symptom production of either the distance of calcification from the lumen or of the percent area occupied by the lipid necrotic core or calcification. The number of macrophages infiltrating the region of the fibrous cap was three times greater in the symptomatic plaques compared with the asymptomatic plaques (1114 +/- 1104 vs 385 +/- 622, respectively, p < 0.009). Regions of fibrous cap disruption or ulceration were more commonly observed in the symptomatic plaques than in the asymptomatic plaques (32% vs 20%). None of the demographic or clinical atherosclerosis risk factors distinguished between symptomatic and asymptomatic plaques. CONCLUSIONS: These findings indicate that proximity of plaque necrotic core to the lumen and cellular indicators of plaque neoformation or inflammatory reaction about the fibrous cap are associated with clinical ischemic events. The morphologic complexity of carotid stenoses does not appear to determine symptomatic outcome but rather the topography of individual plaque components in relation to the fibrous cap and the lumen. Imaging techniques that precisely resolve the position of the necrotic core and evidence of inflammatory reactions within carotid plaques should help identify high-risk stenoses before disruption and symptomatic carotid disease.

Aged

Validation of a new and specific intraoperative measurement of vein graft resistance.

PURPOSE: Clinical studies have revealed that the most important predictor of successful bypass grafting is the origin and quality of the bypass conduit. Attempts at intraoperative evaluation of the hemodynamic properties of the conduit, including assessment of blood flow (Q), pressure gradients (delta P), and resistance (R), have not been useful. This is because each of these parameters measures the characteristics of the graft plus the outflow bed. To date, no specific measurement of the resistive properties of the conduit only is available. The purpose of this investigation was to evaluate longitudinal impedance (ZL) as a measure of conduit-specific resistance and to evaluate its potential in predicting the outcome of infrainguinal vascular reconstructions. METHODS: ZL was measured during surgery in 73 infrainguinal autologous vein reconstructions performed in 68 patients in two separate institutions over a 21-month period. Vein graft ultrasonic transit time Q and delta P (from proximal to distal anastomosis) were measured at baseline and after maximal peripheral vasodilatation with an intraarterial injection of papaverine 30 mg. Waveforms were recorded for 10 seconds at 200 Hz using a digital acquisition system. R was calculated as proximal mean pressure divided by mean blood flow (Q). After Fourier transformation, ZL was calculated as delta P/Q at each harmonic and total ZL (integral of ZL) was defined as the integral of moduli from 0 to 4 Hz. RESULTS: All hemodynamic variables were significantly affected by papaverine vasodilatation (delta P, 3.9 +/- 0.5 vs 6.3 +/- 0.8 mm Hg; Q, 78.2 +/- 7.0 vs 126 +/- 11 ml/min; R, 134 +/- 17 vs 72.7 +/- 6.2 x 10(3) dyne.sec.cm-5; p < 0.0001), except integral of ZL, which remained constant (31.1 +/- 2.8 vs 30.8 +/- 2.8 x 10(3) dyne.cm-5; p = NS). After follow-up of 1 week to 17 months (median, 5 months), the 1-year primary, primary-assisted, and secondary patency rates were 72% +/- 7%, 77% +/- 6%, and 81% +/- 6%, respectively. Using Cox analysis, primary patency was significantly associated with decreased integral of ZL (p = 0.0001), but not with baseline or papaverine-stimulated delta P, Q, delta P/Q, or R integral of ZL > 47 x 10(3) dyne.cm-5 predicted primary failure with 90% positive and negative predictive value. CONCLUSIONS: Intraoperative measurement of integral of ZL in infrainguinal vein grafts is independent of outflow conditions (that is, does not change with papaverine), and hence describes the resistive properties of the conduit only. In addition, these preliminary data suggest that integral of ZL is predictive of short-term primary patency. integral of ZL is the first available hemodynamic measurement that is conduit-specific and may therefore be a better predictor of graft patency than currently available methods.

Aged

Mechanisms of neurologic deficits and mortality with carotid endarterectomy.

OBJECTIVE: To evaluate the incidence and etiology of perioperative complications of carotid endarterectomy. DESIGN: Retrospective review of carotid endarterectomies performed over 13 years. Risk factors, indications, results of electroencephalographic (EEG) monitoring, and outcomes were evaluated. SETTING: University medical center. PATIENTS: Three hundred sixty-seven consecutive primary carotid endarterectomies were performed on 336 patients. Indications for operation included transient ischemic attack (48.5%), asymptomatic stenosis (24%), stroke (17%), nonlateralizing ischemia (9.5%), and stroke-in-evolution (1%). MAIN OUTCOME MEASURES: Postoperative neurologic deficits (permanent and transient) and deaths were correlated with preoperative symptoms, probable mechanism of the neurologic event, intraoperative EEG changes, and the use of intraoperative shunts. RESULTS: Four new permanent neurologic deficits (1.1%) and one transient postoperative deficit were noted. Of the five deficits, three were related to undiagnosed intraoperative cerebral ischemia and two were related to perioperative emboli. Three perioperative deaths (0.8%) occurred: two of myocardial infarction and one of an intracerebral hemorrhage from a ruptured arteriovenous malformation. Intraoperative EEG tracings for the most recent consecutive 175 procedures were analyzed. Shunts were used in 45 patients (26%), 38 of whom demonstrated significant EEG changes with carotid clamping. CONCLUSIONS: Carotid endarterectomy can be performed with a low risk of stroke (1.1%) and death (0.8%). Stroke was due to cerebral ischemia or embolization. With meticulous surgical technique, death is due to myocardial ischemia and not neurologic events.

Adult

Extra-anatomic reconstruction.

Extra-anatomic bypass grafts have proven to be effective in bypassing infected regions, in avoiding hostile abdomens, and in patients with limited life expectancy. The extra-anatomic bypass graft can be used as a temporizing conduit while infected fields are definitively treated. The recommendation to expand the role of extra-anatomic bypass grafts over more direct revascularization with an aortobifemoral artery bypass graft must be critically evaluated. With advances in anesthesia and critical care management, the postoperative mortality for aortobifemoral bypass is 3% to 5%, with an incidence of myocardial infarction of 2%. Long-term primary patency of the aortofemoral bypass graft is 80% to 92% at 5 years. The 5-year primary patency rate for the axillofemoral bypass graft of 50% to 73% does not strongly support the expanded role of extra-anatomic bypass in otherwise healthy patients undergoing aortoiliac bypass. Yet the extra-anatomic bypasses have a vital role in the management of selected patients and should be in the armamentarium of all vascular surgeons.

Arterial Occlusive Diseases

Premedication with oral and transdermal clonidine provides safe and efficacious postoperative sympatholysis.

We studied 61 patients undergoing elective major non-cardiac surgery in a randomized, double-blind, placebo-control clinical trial to test the hypothesis that the addition of clonidine to a standardized general anesthetic could safely provide postoperative sympatholysis for patients with known or suspected coronary artery disease. Patients were allocated randomly to receive either placebo (n = 31) or clonidine (n = 30). The treatment group received premedication with a transdermal clonidine system (0.2 mg/d) the night prior to surgery, which was left in place for 72 h, and 0.3 mg oral clonidine 60-90 min before surgery. Clonidine reduced enflurane requirements, intraoperative tachycardia, and myocardial ischemia (1/28 clonidine patients vs 5/24 placebo, P = 0.05). However, clonidine decreased heart rates only during the first five postoperative hours; the incidence of postoperative myocardial ischemia (6/28 clonidine vs 5/26 placebo) did not differ between the two groups. Patients who experienced postoperative myocardial ischemia tended to have higher heart rates after surgery. Clonidine significantly reduced the plasma levels of epinephrine (P = 0.009) and norepinephrine (P = 0.026) measured on the first postoperative morning. There were no differences in the need for intravenous fluid therapy or antihypertensive therapy after surgery. The number of hours spent in an intensive care setting and the number of days spent in hospital were not different between the two groups. These results suggest that larger doses of clonidine should be investigated for their ability to decrease postoperative tachycardia and myocardial ischemia.

Administration, Cutaneous

Use of the Greenfield filter in patients with major trauma.

Patients with major trauma often cannot be given the benefit of preventive measures such as pneumatic compression boots and low-dose heparin against pulmonary embolism. The Greenfield filter is accepted as a safe and effective method of prophylaxis of this complication. The aim of this study was to evaluate the efficacy of placement of the Greenfield filter in 161 patients with major trauma. Between January 1984 and July 1988, 94 patients with an injury severity score (ISS) of > 16 were treated. This score is predictive of a mortality rate of at least 10% and defines major trauma based on anatomic injury. Some 20% (19 of 94) of these patients developed deep vein thrombosis despite standard prophylactic measures and 8% (eight of 94) suffered pulmonary embolism, two of which were fatal. Pulmonary embolism occurred without antecedent evidence of deep vein thrombosis in another 15% of patients (14 of 94), three of which caused death. From August 1988 until July 1992, of 67 other patients with an ISS > 16, 13% (nine of 67) developed deep vein thrombosis and 1% (one of 67) had a pulmonary embolism; this was not statistically significant (P > 0.25). Of these 67 patients who were considered to be at high risk of pulmonary embolism, because of a contraindication to anticoagulation or physical impediment to sequential compression boots, 29 had prophylactic placement of a Greenfield filter. No pulmonary emboli occurred in these patients. During long-term follow-up (mean 32.8 (range 4-58) months), 84% of the surviving patients (21 of 25) underwent duplex ultrasonography of the inferior vena cava; patency of the vessel was confirmed in all patients.

Adolescent

Carotid patch angioplasty: immediate and long-term results.

To determine the benefit of carotid patch angioplasty, a retrospective study of 1000 consecutive carotid endarterectomies was done. Based on the type of carotid endarterectomy closure, patients were divided into four groups: 250 had primary closure, 250 had expanded polytetrafluoroethylene patch, 250 had Dacron patch, and 250 had saphenous vein patch. On the basis of operative technique or type of carotid artery closure, no statistical difference was found in the incidence of postoperative stroke (p greater than 0.25): primary closure 1.6% (4), expanded polytetrafluoroethylene 2.0% (5), Dacron patch 1.6% (4), and saphenous vein patch (0). Postoperative carotid patency was determined by B-mode ultrasonography, and 717 patients were evaluated in follow-up extending to 6 years (mean 37.8 months). Based on the method of carotid endarterectomy closure, no significant difference (p greater than 0.25) was found in the incidence of significant restenosis (greater than 50% diameter reduction): primary closure 4.0% (7), expanded polytetrafluoroethylene 4.0% (6), Dacron 5.4% (9), and saphenous vein 1.0% (2). Significant restenosis was most frequent in habitual smokers (93%, 25/28) and females (78%, 22/28) despite the method of carotid endarterectomy closure. No statistical difference was found in the incidence of late ipsilateral stroke either (p greater than 0.25): primary closure 2.9% (5), expanded polytetrafluoroethylene 2% (3), Dacron 5% (3), and saphenous vein 0%. These results indicate that the incidence of postoperative stroke, regardless of method of arterial closure, was not statistically different. The method of carotid closure did not appear to affect the occurrence of late ipsilateral stroke or restenosis; however, patch angioplasty with saphenous vein appears appropriate in habitual smokers, and likely in patients with small internal carotid arteries.

Blood Vessel Prosthesis

Connexin43 gene expression in the rabbit arterial wall: effects of hypercholesterolemia, balloon injury and their combination.

The specialized functions of endothelium require intercellular communication between endothelial cells within the monolayer, and between endothelium and other cells present in the vessel wall. This is accomplished by a combination of paracrine soluble mediators and direct gap-junctional intercellular communication (GJIC) mediated by a family of connexin proteins. A prominent connexin expressed by vascular cells in vivo and in vitro is connexin 43 (Cx43). We have investigated the in vivo gene regulation of Cx43 in the context of vascular pathology, as a result of mechanical injury, hypercholesterolemia or both. The aortoiliac bifurcation in the rabbit was examined following three types of insult: (1) diet-induced hypercholesterolemia resulting in macrophage-rich fatty streak lesions, (2) mechanical, stretch-denudation injury resulting in intimal smooth muscle cell (SMC) proliferation and (3) mechanical injury superimposed on hypercholesterolemia resulting in a complex vascular lesion having characteristics of both interventions. The normal rabbit iliac artery expressed approximately equal levels of Cx43 mRNA in the medial SMC layers and in the endothelium. In hypercholesterolemia-induced atherosclerosis, Cx43 expression was most prominent in macrophage foam cells even though normocholesterolemic precursor monocytes did not express Cx43 mRNA. Antibodies directed specifically to Cx43 protein confirmed the expression of macrophage gap junction protein in these cells. Medial SMC in hypercholesterolemia exhibited less Cx43 than their normal counterparts in control animals. Mechanical injury in the absence of hypercholesterolemia resulted in intimal thickening in which Cx43 expression in the intimal SMC was equivalent to that in the subjacent medial SMC, both being approximately equivalent to normal uninjured rabbit medial SMC expression. Cell-specific expression of Cx43 in combined mechanical injury/hypercholesterolemia was similar to that observed in hypercholesterolemia alone: Cx43 upregulation in macrophages, while medial SMC were downregulated. Normo- and hypercholesterolemic alveolar macrophages of the lung and Kupffer cells of the liver did not exhibit induction of Cx43 mRNA, nor did macrophages isolated from peritoneal or bronchial lavage fluid of the same animals. This work extends our previous finding of Cx43 upregulation in human atherectomy tissue and demonstrates that atherosclerotic lesions in situ, in a controlled animal model of atherosclerosis, exhibit cell-specific changes in Cx43 gene expression. Changes in medial SMC migration, proliferation and phenotype, as well as enhanced interactions between adherent/infiltrating monocytes and endothelium may be related to modified GJIC pathways in the vessel wall.

Animals