Antibodies against transforming growth factor-beta 1 suppress intimal hyperplasia in a rat model.

Intimal hyperplasia is induced by therapeutic vascular interventions and often results in clinically important narrowing of the vascular lumen. Examination of the role of TGF-beta 1 in a rat carotid artery injury model confirmed the presence of a previously reported increase in TGF-beta 1 mRNA in the media of injured arteries. Administration of neutralizing anti- TGF-beta 1 antibodies significantly (P < 0.05) reduced the size of the intimal lesions that developed after carotid balloon injury. A control antibody had no effect. The intimal/medial area ratio was also reduced in the anti-TGF-beta 1 group relative to controls (P < 0.01). Immunohistochemical staining showed that two TGF-beta 1-induced extracellular matrix components, EDA + fibronectin and versican, were greatly increased in the untreated neointimal lesions, but were almost completely absent from the lesions of the anti-TGF-beta 1-treated animals. We conclude that TGF-beta 1 is causally involved in the development of intimal hyperplasia, and that anti-TGF-beta 1 agents may be useful in achieving at least partial control of this condition.

Preoperative dipyridamole-thallium scanning, selective coronary revascularization and long-term survival in patients with critical lower limb ischemia.

BACKGROUND: A large proportion of patients with critical limb ischemia have advanced, often asymptomatic coronary artery disease which is associated with increased perioperative risk and decreased long-term survival. METHODS: We evaluated retrospectively the short and long-term effect of routine dipyridamole-thallium cardiac scanning (DTS) and selective coronary revascularization in 113 consecutive patients who were scheduled for revascularization of the lower extremity. RESULTS: DTS was abnormal in 60 (53.1%) patients and demonstrated a moderate-severe reversible defect in 26 (23.0%) patients. On the basis of DTS and clinical evaluation 33 (29.2%) patients were referred for coronary catheterization. Of these, 9 underwent PTCA and 4 underwent coronary artery bypass, without complications. Surgical revascularization of the limbs was performed in all but two patients. Two (1.8%) patients died postoperatively, three (2.7%) sustained nonfatal postoperative myocardial infarctions. None of the patients who underwent preoperative coronary revascularization suffered a cardiac complication after the peripheral vascular operation. During mean follow-up of 31.7 months, 30 (28.0%) patients died. A moderate-severe reversible defect on DTS was the strongest predictor for shortened survival (Exp(b)=0.61, CI 95%=0.42-0.88; p=0.006). Patients who underwent preoperative coronary revascularization followed a survival curve approaching those without a reversible defect on DTS (mean survival 61+/-8 vs 63+/-4 months; NS) which was significantly better than those with such a defect who did not undergo coronary revascularization (mean survival 34+/-5 months; p=0.03). CONCLUSIONS: While the perioperative benefits of routine preoperative DTS screening in patients with critical limb ischemia, remain debatable, it provides an opportunity for identification and treatment of life-limiting coronary artery disease and improving survival.

Ultrasound-guided thrombin injection for the treatment of iatrogenic pseudoaneurysm of the femoral artery.

BACKGROUND: Pseudoaneurysm occurring after catheterization of the femoral artery is associated with significant morbidity. Percutaneous ultrasound-guided thrombin injection has recently emerged as a potential first-line therapy. OBJECTIVES: To evaluate the efficacy of this treatment in eight patients with iatrogenic femoral artery pseudoaneurysm. METHODS: After attempted treatment with external compression had failed, eight patients with iatrogenic femoral artery pseudoaneurysm were treated with thrombin injection. Treatment performed between 2 and 9 days following arterial puncture. The study group comprised seven males and one female ranging in age from 23 to 89 years (median 70). Seven had undergone cardiac catheterization with or without intervention, and five were receiving antiplatelet and/or anticoagulant drugs. Arterial pseudoaneurysm resulted from femoral vein catheterization in one patient. Using a sterile technique and real-time Doppler ultrasound guidance, a dilute solution of bovine thrombin (average dose 250 units, range 100-600), was slowly injected directly into the pseudoaneurysm until cessation of flow was seen. Patients were allowed to walk within 2 hours of the procedure and were followed up clinically and by color Doppler ultrasound during the admission. RESULTS: Cardiac catheterization had been inadvertently performed via the superficial or profunda femoris arteries in four of the eight patients. Thrombin injection was initially successful in all eight patients without complication. Thrombosis occurred immediately in every case. Early recanalization of pseudoaneurysm occurred in one patient despite repeat thrombin injection and attempted ultrasound-guided compression. He eventually required surgical repair. The final success rate was 87.5% (7/8). CONCLUSION: Faulty puncture technique is an important risk factor for the development of post-catheterization femoral artery pseudoaneurysm. Ultrasound-guided thrombin injection is a safe, rapid, well-tolerated, inexpensive and successful therapy. If initial external compression with a sandbag fails to result in thrombosis of the pseudoaneurysm then thrombin injection should be considered as first-line therapy. If unsuccessful, it does not preclude the use of alternative treatment modalities. Further study is necessary to assess the long-term effects of thrombin injection.

Ischemic monomelic neuropathy: an under-recognized complication of hemodialysis access.

During the past 3 years six episodes of ischemic monomelic neuropathy (IMN) have been identified in five patients as a complication of upper extremity dialysis grafts. All patients had long-standing insulin-dependent diabetes, peripheral neuropathy, and brachial artery graft origins, whereas 60% had peripheral vascular disease. Five episodes occurred immediately after graft placement, whereas one was due to a graft-related thromboembolus. Diagnostic delay was common with initial findings attributed to anesthesia, positioning, or surgical trauma. Electrophysiologic studies showed underlying diabetic neuropathy with severe multifocal neuropathy distal to the grafts. Digital pressure indices were reduced but there was no critical ischemia. In three cases ischemia was completely corrected with improvement in one. One patient had proximal balloon angioplasty with no improvement and of the two untreated patients, one improved slightly. Ischemic monomelic neuropathy is a rare but disabling complication of dialysis access in diabetic uremic patients. Its occurrence is unpredictable and diagnostic delay is common. Correction of ischemia is indicated but usually does not improve the neuropathy. Prevention requires further research to more accurately characterize the patients at risk.

Dependence of oxygen consumption on cardiac output in sepsis.

We studied the relationship between oxygen consumption (Vo2) and cardiac output in 17 hemodynamically stable, septic and eight nonseptic ICU patients. Each received 300 ml of fresh-frozen plasma or 25% albumin with up to 500 ml of crystalloids, in addition to regular maintenance fluids; this treatment increased pulmonary wedge pressure (WP) by 3 to 4 mm Hg. Measurements were performed before and after approximately 5 h of volume loading. Because cardiac index (CI) decreased as WP increased in four septic and three nonseptic patients, we grouped the data according to the state of flow instead of the recording time sequence. From low to high flows, mean CI increased in septic patients and nonseptic patients. Oxygen delivery (Do2) increased in septic and nonseptic patients. Vo2 remained unchanged in nonseptic patients, while it increased in septic patients. Accordingly, arteriovenous oxygen difference narrowed in nonseptic patients from 4.46 +/- 1.62 to 3.59 +/- 1.21 ml/dl (p less than .05) but did not change in septic patients. In the septic group, the difference in CI between high and low flows was significantly (p less than .05) greater in survivors than in nonsurvivors. We conclude that the septic state is accompanied by a peripheral oxygen deficit, which can be partially reversed by maintaining an above-normal CI and Do2.

Vascular smooth muscle cells from injured rat aortas display elevated matrix production associated with transforming growth factor-beta activity.

The arterial response to injury is characterized by a short period of increased proliferation and migration of vascular smooth muscle cells, followed by an extended period of extracellular matrix accumulation in the intima. Transforming growth factor-beta (TGF-beta) has been implicated as a causative factor in the formation of extracellular matrix in this process, which leads to progressive thickening of the intima, known as intimal hyperplasia. In vitro analysis of vascular smooth muscle cells harvested from normal rat aortas and from aortas injured 14 days earlier showed that both types of cells attached equally well to culture dishes but that the initial spreading of the cells was increased in cells derived from injured vessels. Cells from the injured arteries produced more fibronectin and proteoglycans into the culture medium than the cells from normal arteries and contained more TGF-beta 1 mRNA. TGF-beta 1 increased proteoglycan synthesis by normal smooth muscle cells, and the presence of a neutralizing anti-TGF-beta 1 antibody reduced proteoglycan synthesis by the cells from injured arteries in culture. Fibronectin synthesis was not altered by these treatments. These results indicate that the accumulation of extracellular matrix components in neointimal lesions is at least partially caused by autocrine TGF-beta activity in vascular smooth muscle cells.

Does complete aneurysm exclusion ensure long-term success after endovascular repair?

PURPOSE: To examine whether complete aneurysm exclusion is a reliable marker for successful long-term endovascular abdominal aortic aneurysm (AAA) repair. METHODS: The medical records, computed tomographic (CT) scans, and duplex examinations of all the patients who underwent endovascular AAA repair at a single institution and had at least 12 months of follow-up were reviewed. Sixty-seven patients (58 men; mean age 74 years, range 57-87) were identified. Complete aneurysm exclusion was defined by the absence of an endoleak at any time before an adverse event. The primary endpoint included all major adverse events that occurred during the postoperative period, including aneurysm expansion, acute symptoms referable to the AAA, late secondary procedures, ruptures, and deaths from ruptures and all other causes. RESULTS: There were 44 adverse events (8 expanding aneurysms, 4 acute symptoms, 17 secondary procedures, and 15 deaths from other causes) in 28 (42%) patients. Among 36 (54%) patients who had initial complete aneurysm exclusion (no endoleak), 12 (33%) experienced adverse events, compared with 16 (52%) events in 31 patients who had endoleak (chi2 = 1.59, p = 0.21). CONCLUSIONS: There was no statistically significant difference in adverse events based on the presence or absence of endoleak. Complete aneurysm exclusion as defined by absence of an endoleak does not indicate an event-free postoperative course. A better marker of clinical success of endovascular AAA repair is needed.

Nitroglycerin decreases medial smooth muscle cell proliferation after arterial balloon injury.

PURPOSE: Nitroglycerin and its effector molecules nitric oxide and cyclic guanosine monophosphate decrease smooth muscle cell proliferation in vitro. We examined the in vivo effect of nitroglycerin on intimal hyperplasia. METHODS: We treated rats after carotid artery balloon injury with nitroglycerin delivered paraarterially with a miniosmotic pump for 1 week. RESULTS: High nitroglycerin serum levels were achieved, and the level of cyclic guanosine monophosphate in the carotid artery wall was significantly increased (1.48 +/- 0.37 vs 0.86 +/- 0.39 pmol/mg protein; p < 0.05) in the nitroglycerin-treated group. Cellular proliferation in the arterial wall was assessed by incorporation of 5-bromo-2'-deoxyuridine 6 days after the injury and was lower in the nitroglycerin-treated group (15.2 +/- 3.4 vs 36.3 +/- 5.5 positive cells/section; p < 0.005). This was due to a decrease in the number of proliferating cells in the media (6.3 +/- 1.2 vs 21.8 +/- 4.5; p < 0.005), whereas in the budding neointima, the difference in the number of proliferating cells was not significant. Neointimal lesions 21 days after the injury did not differ in cross-sectional intimal area, in intimal/medial area ratio, and in cell density. CONCLUSION: Nitroglycerin decreased medial cellular proliferation after balloon injury and had no significant effect on intimal proliferation. The size of the neointimal lesion was not affected by nitroglycerin therapy.

Steroid therapy and duodenal ulcer in infants.

Two infants with acute life-threatening complications of duodenal ulcer following steroid administration are described. Although the possible association between steroid therapy and peptic ulcer disease is well known, the need for ulcer prophylaxis during such therapy in infants is not unanimously accepted. The case for ulcer prophylaxis in this setting is presented.

Surgical treatment of aneurysm of the persistent sciatic artery.

Persistent sciatic artery (PSA) is a rare congenital malformation that is complicated by aneurysm formation in more than 25% of the reported cases. Two cases of aneurysm of the PSA are presented. Twenty-six aneurysms of the PSA, including our two cases, have been reported in the English literature in the last three decades. Early surgical treatment is warranted to decrease the 25% amputation rate associated with thromboembolic complications. The posterior, transgluteal repair of this aneurysm affords excellent exposure and avoids a long bypass graft, multiple incisions, and staged procedures. Magnetic resonance imaging may be helpful in preoperative evaluation of the feasibility of proximal, extrapelvic vascular control.

Infection of a ruptured aortic aneurysm and an aortic graft with bacille Calmette-Guérin after intravesical administration for bladder cancer.

A case of aortic graft infection with bacille Calmette-Guérin (BCG) is described. The graft was placed during urgent repair of a ruptured abdominal aortic aneurysm 2 years after intravesical administration of BCG for grade II transitional cell carcinoma of the bladder with associated carcinoma in situ. At the time of operation, no gross evidence of infection was found and pathologic examination of the aortic wall was unremarkable. Aortic graft infection with BCG was diagnosed 1 year after placement of the graft. Retrospective examination of formalin-fixed, paraffin-embedded aortic wall and thrombus removed at the time of graft placement by the polymerase chain reaction technique demonstrated the presence of mycobacterial DNA. The patient's condition improved with medical therapy during an observation period of 18 months with near total resolution on computed tomography scanning. Ultimately (20 months later), an aortoenteric fistula developed that required graft removal and axillobifemoral bypass.

Screening for abdominal aortic aneurysms during lower extremity arterial evaluation in the vascular laboratory.

PURPOSE: The purpose of this study was to evaluate the cost-effectiveness of screening for abdominal aortic aneurysms (AAA) during noninvasive lower extremity arterial examination in the vascular laboratory. METHODS: Over 30 months we screened 531 patients who underwent lower extremity arterial evaluations in the vascular laboratory. The patients had fasted overnight, and, after the regular noninvasive lower extremity arterial examination, the abdominal aorta was screened with B-mode ultrasonography. RESULTS: The aorta was adequately visualized in 475 patients (89%). Mean aortic diameter was 19.6 +/- 4.1 mm at the juxtarenal level and 18.8 +/- 7.2 mm in the lower infrarenal aorta. The aortic diameter was larger in men (p < 0.001) and in smokers (p < 0.001). AAA (diameter greater than 3.0 cm) were identified in 32 patients (6.0% of the 531 patients screened), and 15 of the aneurysms were equal to or larger than 4.0 cm. The best predictors for AAA by logistic regression analysis were male sex (p < 0.005), advanced age (greater than 65 years, p < 0.01), and a history of smoking (p < 0.01). The prevalence of AAA was 6.7% (32/475) in the population in whom the aorta was visualized and 15.2% (19/125) in male smokers over 65 years of age. Aneurysms of 4.0 cm or greater were identified in 3.2% of the entire population screened and 8.8% of male smokers over age 65. Limited aortic scanning prolonged the vascular laboratory examination by an average of 5 minutes. Thus detection of one aneurysm required 83 minutes of scanning time for the whole population studied and 36 minutes of scanning of male smokers over age 65, at a cost of $240 to $553 per aneurysm identified. CONCLUSION: Screening for AAA during lower extremity arterial evaluation in the vascular laboratory addresses a high-risk population, is cost-effective, and should be considered an appropriate and valuable addition to the examination protocol.

Results of reconstruction in major pelvic and extremity venous injuries.

PURPOSE: Outcome and venous patency after reconstruction in major pelvic and extremity venous injuries was studied. METHODS: We retrospectively reviewed 46 patients with 47 venous injuries. RESULTS: Injuries were caused by penetrating trauma in 37 extremities, blunt trauma in 6 patients, and were iatrogenic in 4 patients. Pelvic veins were injured in 4 patients, lower-extremity veins were injured in 39 limbs in 38 patients, and upper-extremity veins were injured in 4 patients. Concomitant arterial injuries occurred in 37 patients. Venous repairs were mostly of the complex type and included spiral or panel grafts in 15 (32%) reconstructions, interposition grafts or patch venoplasty in 19 (40%) reconstructions, end-to-end and lateral repair in 11 patients, and ligation in 2 patients. Two patients underwent early amputation. Early transient limb edema occurred in 2 patients, and postoperative venous occlusions were documented in 4 patients. Full function was regained in 39 (81%) extremities. No variable, including 4 retrospectively applied extremity injury scores (mangled extremity severity score [MESS], limb salvage index [LSI], mangled extremity syndrome index [MESI], predictive salvage index [PSI]), correlated with outcome. High values on all 4 scores were significantly associated with reexplorations (P <.02), which were done in 8 patients for debridement (5), arrest of bleeding (2), and repair of a missed arterial injury (1). Follow-up of 28 +/- 6 months on 27 patients (57%; duplex scan in 18, continuous-wave Doppler and plethysmography in 9, and venography in 3) showed 1 occlusion 6 weeks after the injury and patency of all other venous reconstructions. CONCLUSION: Reconstructions of major venous injuries with a high rate of complex repairs result in a large proportion of fully functional limbs and a high patency rate. A high extremity injury score predicts the need for reexploration of the extremity. Mostocclusions occur within weeks of injury, and the subsequent delayed occlusion rate is very low.

Mesenteric bypass for chronic mesenteric ischaemia.

Chronic mesenteric ischaemia is an uncommon disease that requires treatment to relieve the symptoms of abdominal angina and to prevent intestinal infarction. Over a period of 3 years, 12 patients with visceral artery stenosis or occlusion were referred to the authors' service and 10 underwent mesenteric bypass grafting. Both the coeliac and the superior mesenteric arteries were revascularized in four patients, and the superior mesenteric artery alone in six patients, using a variety of grafts and graft configurations. This was done in conjunction with aortic graft placement in four cases and with renal bypass in three. All patients survived the procedure. At a mean follow-up of 28 months, one patient died of myocardial infarction 42 months after surgery, while all survivors are symptom-free. Chronic mesenteric ischaemia can be treated safely and effectively. The variation in the pattern of mesenteric occlusions and the frequent association with aortic and renovascular disease does not allow for a single 'best' technical solution but requires the surgical procedure to be individually tailored.

Thoraco-abdominal enteric duplication with meningocele, skeletal anomalies and dextrocardia.

We describe an infant with an enteric thoraco-abdominal duplication arising in the proximal jejunum and associated with a dorsal meningocele, dextrocardia, agenesis of ribs and hypoplasia of the left arm. Diagnosis was reached post-operatively and the infant died of cytomegalovirus pneumonitis. Results of the postmortem examination are presented. Awareness of this rare malformation is required in order to reach a timely diagnosis and to plan a suitable operative approach.

Arterial trauma of the upper extremity in children.

Thirty children with upper extremity arterial trauma were retrospectively reviewed. Trauma was penetrating in 87% of cases and in 53% injury was caused by broken plate glass. The injured artery was repaired in all but four cases. Nerves were injured in 53% and tendons in 23%. All severed nerves and tendons were repaired primarily. Postoperatively three children with proximal injuries had no palpable pulse in the affected extremity. One patient died of underlying disease and another required amputation during initial surgery due to extensive soft-tissue injury. Followup revealed no dysfunction directly related to vascular insufficiency. Neurologic deficit was found in 33% of the children followed, but only in one was the limb totally nonfunctional. We conclude that the long-term outcome is largely dependent upon neurologic injury. Glass doors and large glass windows should be avoided in the vicinity of children's play areas.