J.Jeffrey Alexander

The effects of thrombin on bovine aortic endothelial and smooth muscle cells

Recent evidence suggests that thrombin interacts with various cell types, stimulating cellular proliferation and protein and prostanoid production. To further delineate its role in vascular healing, we have studied the effects of thrombin on proliferation and matrix production by the cells of the vessel wall. The addition of thrombin (1 unit/ml) to cultures of bovine aortic smooth muscle cells resulted in an increase in cell proliferation (p less than 0.01) and number (p less than 0.03), whereas in cultures of bovine aortic endothelial cells thrombin produced a decrease in cell proliferation (p less than 0.01) and number (p less than 0.02). Thrombin also altered matrix composition in cultures of these cells. In both bovine aortic endothelial cells and bovine aortic smooth muscle cell cultures grown in the presence of thrombin, total protein content was significantly increased when compared to controls (p less than 0.03). In bovine aortic endothelial cell cultures the addition of thrombin resulted in a decrease in collagen content (p less than 0.01) and an increase in sulfated glycosaminoglycan content (p less than 0.02). In contrast, in bovine aortic smooth muscle cell cultures thrombin resulted in an increase in collagen content (p less than 0.03), whereas glycosaminoglycan content was unaffected. These findings suggest that thrombin may significantly influence vascular healing and function by altering cell number and matrix composition.

Is deep vein thrombosis surveillance warranted in high-risk trauma patients?

BACKGROUND Deep vein thrombosis (DVT) has been reported to occur in 20% to 40% of high-risk trauma patients if no prophylaxis is used. The purpose of this study was to determine the incidence of DVT and utility of a screening program in a high-risk group of trauma patients for whom routine DVT prophylaxis was utilized. PATIENTS AND METHODS Of 3,154 trauma admissions over a 20-month period, 343 patients (10.9%) identified as high risk based on established criteria (prolonged bed rest, Glasgow coma score (GCS) of 7, spinal injury, lower extremity or pelvic fracture) were placed on a prospective surveillance protocol using color-flow duplex scanning and received thromboembolic prophylaxis. RESULTS Twenty-three thromboembolic complications occurred, including 20 DVTs (5.8%) and 3 pulmonary emboli ([PE] 1%). Univariate analysis showed that the risk of DVT was related to age (52.6 + 19.9 years versus 38.1 + 18.5; P = 0.001), a longer hospital stay (31.4 versus 17.8 days; P = 0.001), or the presence of spinal fracture (12.6% versus 3.5%; P = 0.01). Discriminant function analysis revealed that length of stay, intensive care unit days, age, and GCS allowed correct classification of those who did not develop DVT in 97% of cases but was only correct in 15% of cases in predicting those who would develop DVT. Injury severity score (ISS) was not predictive in this multivariate analysis. Seventeen (85%) DVTs were unsuspected clinically. Study patients received an average of 3.5 studies at an overall charge of

The management of localized abdominal aortic dissections

313,330 to detect 17 clinically unsuspected DVTs (5%). This represents about 5% of the total bed charges for these patients, or

Infrainguinal bypass in patients with end-stage renal disease

18,000 per DVT. CONCLUSIONS These results suggest that standard use of DVT prophylaxis in a high-risk trauma population leads to a low incidence of DVT and that a screening protocol is effective in detecting unsuspected DVTs. Use of a surveillance protocol, however, may reduce but will not eliminate the incidence of pulmonary emboli in this patient population.

Etiology and diagnosis of bilateral leg edema in primary care

Aortic dissections limited to the abdominal aorta occur infrequently. We have identified four cases of abdominal aortic dissection and have reviewed these in combination with 43 previously reported cases to identify factors that influence the prognosis and management of this disease. Abdominal aortic dissections are similar to thoracic dissections in their presentation, with acute shearing pain and systolic hypertension occurring commonly. Although the diagnosis may be made by ultrasonography or CT scanning, angiography is the definitive diagnostic study. Factors found to be associated with high mortality include presentation with acute pain (p less than 0.0003), involvement of visceral vessels (p less than 0.02), and rupture (p less than 0.000002). Chronicity appears to be protective (p less than 0.04), although chronic dissections may present acutely. Although prosthetic replacement of the involved aorta is the treatment of choice in most cases, nonoperative management with regular follow-up can be considered in asymptomatic chronic dissections.

Is the increasing use of prophylactic percutaneous IVC filters justified

BACKGROUND This study was undertaken to evaluate the outcome of infrainguinal arterial reconstruction in a high-risk subset of patients with end-stage renal disease. METHODS We reviewed the medical records of 44 patients requiring maintenance dialysis and undergoing 57 infrainguinal bypass procedures for limb salvage from 1986 to 1992. These included 16 (28%) femoropopliteal and 41 (72%) tibial or pedal bypasses with autogenous (82%), prosthetic (12%), or composite (6%) graft materials. The principal indications for operation were ischemic ulceration or gangrene (79%) and rest pain (21%). Angiographic evaluation most frequently showed single-vessel runoff (56%). Risk factors included age (mean, 63 years), diabetes (75%), hypertension (93%), coronary artery disease (52%), smoking (39%), previous myocardial infarction (20%), and contralateral amputation (18%). Infection was present in 22 limbs (39%). RESULTS Early (30-day) surgical morbidity rate was 39%, including wound breakdown (19%), graft thrombosis (9%), and major amputation (4%). Perioperative mortality rate was 9%. Cumulative primary graft patency rates were 71% and 63%, secondary patency rates were 80% and 66%, and limb salvage rates were 70% and 52% at 1 and 2 years, respectively. Limb loss correlated most highly with the presence of preoperative infection (p = 0.036; log-rank method). Patient survival rate was 52% at 2 years. CONCLUSIONS Life-table analysis confirms a poor life expectancy for this population but indicates that an acceptable level of limb salvage may be achieved with arterial reconstruction in properly selected patients.

Oxygen delivery is an important predictor of outcome in patients with ruptured abdominal aortic aneurysms.

PURPOSE To identify the causes of bilateral leg edema in a primary care setting, and to determine the ability of primary care providers to arrive at the correct diagnosis using the information available at the initial clinical encounter. PATIENTS AND METHODS Fifty-eight ambulatory adult patients with bilateral leg edema were enrolled at an inner city family practice during a 3-year period. Historical information, physical examination findings, and clinical impressions of primary care providers were compared with the results of laboratory evaluations consisting of echocardiograms, venous duplex ultrasound leg scans, serum albumin levels, and when appropriate, 24-hour urinalyses. RESULTS Forty-five patients (78%) completed the study. The initial clinical impression was venous insufficiency in 32 (71%) patients and congestive heart failure in 8 (18%) patients. In actuality, 15 (33%) patients had a cardiac condition as a cause of their leg edema, and 19 (42%) had pulmonary hypertension. All of the patients with heart disease, and almost all of those with pulmonary hypertension, were age 45 years or older. Only 10 (22%) of the subjects had venous insufficiency. Renal conditions, medication use, and hypoalbuminemia were less common. CONCLUSIONS Utilizing clinical information only, many patients with cardiopulmonary pathology were incorrectly diagnosed as having more benign conditions, most commonly venous insufficiency. Echocardiographic evaluation, including an estimation of pulmonary artery pressure, may be advisable in many patients with bilateral leg edema, especially if they are at least 45 years old.

Outcome of complex vascular and orthopedic injuries of the lower extremity

To determine whether the ease of percutaneous inferior vena cava (IVC) filter placement has led to an alteration of procedural indications, we reviewed the medical records of 150 patients who underwent 156 filter insertions from January 1986 through June 1993. Thirty-nine Greenfield filters were surgically inserted, while 117 percutaneous devices were placed in 111 patients. A comparison of these two groups showed that they had similar thromboembolic risks. Indications for surgical filter placement included pulmonary embolism (PE) prophylaxis (23%), PE with a contraindication to anticoagulation therapy (28%), and complication (26%) or failure (20%) of anticoagulation therapy. Indications for initial percutaneous placement included PE prophylaxis (56%), PE with a contraindication to anticoagulation therapy (27%), and complication (7%) or failure (9%) of anticoagulation therapy. Early mortality in the surgical and percutaneous groups was 26% and 27%, respectively. Ten percent of early deaths in the surgical group and 50% in the percutaneous group were associated with prophylactic insertions (P = 0.032). Associated morbidity was 8% in the surgical versus 24% in the percutaneous group (P = 0.036). The unrestricted use of prophylactic percutaneous IVC filters appears to have resulted in an increased procedure-related morbidity with no clear benefit in early patient survival. These findings suggest a need for improved patient selection.

The effect of nifedipine on lipid and monocyte infiltration of the subendothelial space

OBJECTIVE The purpose of this study was to evaluate the relation of oxygen delivery (DO2) to the occurrence of multiple organ dysfunction (MOD) in patients with ruptured abdominal aortic aneurysms (AAA). SUMMARY BACKGROUND DATA Patients with ruptured AAA are at high risk for the development of MOD and death. Previous reports of high-risk general surgical patients have shown improved survival when higher levels of DO2 are achieved. METHODS Hemodynamic data were collected at 4-hour intervals on 57 consecutive patients (mean age, 70.5 years) who survived 24 hours after repair of infrarenal ruptured AAA. Patients were resuscitated to standard parameters of perfusion (pulse, blood pressure, urine output, normal base deficit). MOD was determined based on six organ systems. Standard parametric (analysis of variance, t tests) and nonparametric (chi square, Wilcoxon) tests were used to compare hemodynamic data, red blood cell requirements, colon ischemia, and organ failure for patients with and without MOD. RESULTS Patients who developed MOD had a significantly lower cardiac index and DO2 for the first 12 hours; the difference was most significant at 8 hours. Logistic regression analysis demonstrated that the strongest predictors of MOD were DO2, early onset of renal failure, and total number of red blood cells transfused. CONCLUSIONS DO2 is an earlier and better predictor of MOD after ruptured AAA than previously identified risk factors. Failure to achieve a normal DO2 in the first 8 hours after repair is strongly associated with the development of MOD and a high mortality. Strategies to restore normal DO2 may be useful to improve outcome in these high-risk patients.

Atherosclerotic aneurysm formation in an in situ saphenous vein graft

Thirty-two patients undergoing limb salvage procedures for complex vascular and orthopedic injuries of the lower extremity were studied in order to identify prognostic indicators for delayed amputation in this select group. A high incidence of nerve (38%), soft tissue (66%), and remote injury (47%) was noted. A comprehensive and integrated approach to vascular, orthopedic, and plastic reconstruction was utilized. Of the 32 patients studied, 1 (3.1%) died as a result of remote injury and sepsis. Amputation was required in 9 patients (28%), while 13 (56%) of the patients with limb salvage showed persistent functional or neurologic deficits. Infection was the most significant factor associated with amputation (p less than 0.0005) and was not avoided by the perioperative use of antibiotics. Delayed amputation resulted in a significant extension of total hospitalization (p less than 0.005). The authors favor an aggressive approach to limb salvage with IIIC injury but recommend early amputation in the presence of significant nerve disruption. An attentive use of tissue debridement, intravenous antibiotics, and early wound coverage is needed to limit infection.