Marcel Scheinman

Upper extremity deep venous thrombosis and its impact on morbidity and mortality rates in a hospital-based population

PURPOSE Although much attention has been focused on lower extremity deep venous thrombosis (LEDVT), there is a relative paucity of data regarding the impact of upper extremity deep venous thrombosis (UEDVT) on morbidity and mortality rates. To increase our knowledge with the latter disease, we have reviewed our experience at our institution with 170 patients who had brachial, axillary, and subclavian vein thromboses. METHODS Over the past 5 years, UEDVT was diagnosed in 170 patients by duplex scanning. The indications for duplex examination were either upper extremity swelling (95%) or as part of the workup for pulmonary embolism (5%). There were 103 women (61%) and 67 men (39%), with ages ranging from 9 to 101 years (mean, 68 +/- 17 years). The diagnosis was made in 152 patients (89%) while they were admitted to the hospital and in 18 patients (11%) in the outpatient clinic. Risk factors included presence of a central venous catheter or pacemaker in 110 patients (65%), malignancy in 63 patients (37%), concomitant LEDVT in 19 patients (11%), and history of LEDVT in 18 patients (11%). Fifty-six patients (33%) had multiple risk factors, whereas 36 patients (21%) had no obvious risk factor. RESULTS The 1-month and 3-month mortality rates for the entire study group were 16% and 34%, respectively. Patients who had concomitant LEDVT, were 75 years of age or older, and were not treated with anticoagulation medication had a significantly higher 1-month mortality rate. Patients whose diagnoses were made in the outpatient setting were statistically younger and had a lower 3-month mortality rate when compared with the patients whose diagnoses were made as inpatients. Pulmonary embolism was documented by ventilation/perfusion scan in 12 patients (7%). Although no patient in the group in which UEDVT was diagnosed on an outpatient basis was documented to have a pulmonary embolism and 12 patients (8%) in the inpatient group had pulmonary emboli, this difference was not statistically significant. Anticoagulation medication did not totally prevent pulmonary embolism in this review. All patients were followed-up for between 0 to 49 months (mean, 13 +/- 1 months). No swelling of the affected arm was observed in 145 patients (94%); four patients complained of mild intermittent swelling (2%), and seven patients reported significant swelling (4%). CONCLUSIONS Contrary to previous reports, these data suggest that UEDVT is associated with a low incidence of postthrombotic upper extremity swelling, but a significant incidence of pulmonary embolism and rate of mortality. This review suggests that UEDVT is at least as serious a disease entity as LEDVT and should be managed as aggressively as LEDVT.

Upper extremity versus lower extremity deep venous thrombosis

BACKGROUND In contrast to lower extremity deep venous thrombosis (LEDVT), it is widely believed that upper extremity deep venous thrombosis (UEDVT) is associated with minimal morbidity or mortality. METHODS In an attempt to compare the two disease processes with respect to pulmonary embolism and mortality, we have reviewed records and performed interviews of 430 patients with LEDVT and 52 patients with UEDVT presenting to our institution between January 1994 and June 1995. RESULTS Pulmonary embolism was documented by ventilation/perfusion lung scan in 9 of 52 patients (17%) with UEDVT and 33 of 430 patients (8%) with LEDVT (P <0.05). Twenty-five of the UEDVT patients (48%) died within 6 months of the diagnosis of UEDVT. Conversely, 14 patients (13%) in the LEDVT group died within 6 months of the diagnosis of LEDVT (P <0.0002). CONCLUSION Contrary to previous reports, this study suggests that UEDVT is associated with a higher morbidity and mortality as compared with LEDVT. These data show that UEDVT has been an underrecognized predictor of morbidity and mortality.

Saphenous vein thrombophlebitis (SVT): A deceptively benign disease

PURPOSE The association between deep vein thrombosis (DVT) and the hypercoagulable state is a well-established entity. However, the association between saphenous vein thrombophlebitis and coagulation abnormalities has not been investigated. Although thrombosis of varicose veins typically runs a benign course, phlebitis of the saphenous system may propagate to the deep system or saphenofemoral junction that requires more aggressive therapy. Given the potential similarity in clinical outcome between saphenous vein thrombophlebitis (SVT) and DVT, we have investigated the coagulation profile of patients presenting with isolated SVT. METHODS Seventeen consecutive patients who presented to our vascular laboratory with isolated SVT had a coagulation profile performed that included antithrombin III (AT III), protein C (PC), protein S (PS) antigen and activity levels, activated protein C (APC) resistance, factor V DNA mutation, and coagulation factors II and X. All patients had duplex scans performed on both the superficial and deep venous systems. Patients with SVT only were treated with nonsteroidal antiinflammatory drugs (NSAIDs) and warm soaks as outpatients, whereas those patients found to have DVT or a clot at the saphenofemoral junction were fully anticoagulated with heparin and coumadin therapy. All 17 patients had at least one repeat coagulation profile performed up to 5 months after their SVT occurrence to ensure that the results of hypercoagulability were not transient. RESULTS Ten (59%) of the 17 patients with SVT had abnormal coagulation profiles on initial presentation. All 10 patients who were hypercoagulable had repeat tests and 6 (35%) remained abnormal. Four patients who had abnormal results converted to normal values. Seven patients with normal coagulation profiles on initial presentation had repeat tests and all remained normal. CONCLUSION The incidence of the hypercoagulable state in patients with SVT is high. Thirty-five percent of patients with isolated SVT had consistently abnormal coagulation profiles. Patients with SVT may be prone to the development of DVT or saphenofemoral junction thrombophlebitis and should be closely followed after the initial diagnosis of hypercoagulability.

Combined coronary artery bypass grafting and abdominal aortic aneurysm repair

BACKGROUND We report here the results of combined coronary artery bypass grafting (CABG) and abdominal aortic aneurysm (AAA) repair and the factors associated with higher mortality following this procedure. METHODS The authors performed a retrospective chart review of 26 patients who underwent combined CABG and AAA repair between March 1990 and October 1996. RESULTS No postoperative myocardial infarction or major cardiac complications were noted. A morbidity rate of 38% (n = 10) and mortality rate of 11% (n = 3) were noted. Comparative analysis of nonsurvivors (n = 3) versus survivors (n = 23) revealed the following: ejection fraction (EF) was significantly lower (33% +/- 3% versus 44% +/- 14%, P < 0.05), duration of cardiopulmonary bypass (CPB) was significantly longer (239 +/- 122 minutes versus 141 +/- 54 minutes, P < 0.05), and incidence of postoperative respiratory failure (67% versus 17%, P = 0.001) were significantly higher in nonsurvivors. No differences in mean age, gender distribution, incidence of hypertension or diabetes were noted between the groups. CONCLUSIONS Combined CABG and AAA repair protected patients from postoperative aneurysm rupture and myocardial infarction. Poor EF, prolonged CPB, and postoperative respiratory failure were associated with higher mortality.

The effect of tumor necrosis factor binding protein and interleukin-1 receptor antagonist on the development of abdominal aortic aneurysms in a rat model ☆ ☆☆ ★ ★★

PURPOSE Tumor necrosis factor (TNF), interleukin 1 (IL-1), and matrix metalloproteases have been noted to be elevated in human abdominal aortic aneurysms (AAAs) as compared with normal and occlusive aortic disease. Because TNF and IL-1 have been shown to cause release of proteases that weaken the aortic matrix, it has been suggested that these cytokines may play a central role in the aortic dilatation process. To substantiate this hypothesis, we investigated the effects of TNF and IL-1 antagonists, tumor necrosis factor binding protein (TNF-BP) and interleukin-1 receptor antagonist (IL-1RA), on the development of AAAs in a well-described rat model. METHODS Isolated segments of infrarenal aorta of 16 rats were perfused with porcine elastase. In the treated group, eight rats were given intravenous TNF-BP prior to elastase perfusion, at 48 hours and at 96 hours. In the control group, eight rats were given only intravenous vehicle at the same time intervals. Isolated segments of infrarenal aorta of an additional 16 rats were perfused with porcine elastase in a similar fashion. In the treated group, eight rats were given intraperitoneal IL-1RA prior to celiotomy and every eight hours. In the control group, eight rats were given only intraperitoneal vehicle at the same time intervals. On the sixth postoperative day, all rats underwent celiotomy and measurement of the infrarenal aortic diameter with a micrometer while the animal was alive. Aortic specimens were collected on day six for hematoxylin and eosin staining, trichrome staining, and gel polyacrylamide gel electrophoresis (PAGE) zymography. RESULTS TNF-BP was completely able to block post elastase dilation, whereas IL-1Ra seemed to have no effect. Hematoxylin and eosin staining and trichrome staining revealed that animals treated with TNF-BP had less of an inflammatory response and preservation of the elastin and smooth muscles in the media of the aortic wall as compared with animals treated with IL-1RA or vehicle. Zymography was not able to detect significant protease activity in the aortic wall of any of the rats at six days. CONCLUSION TNF-BP, but not IL-1RA, may inhibit the development of AAAs in this model.

P53 gene transfer to the injured rat carotid artery promotes apoptosis

BACKGROUND In a previous study we have demonstrated significant reduction of intimal hyperplasia after adenovirus-mediated gene transfer of p53 protein to the injured rat carotid artery. The purpose of this study was to elucidate whether apoptosis is one of the mechanisms responsible for this reduction. Apoptosis, a physiologic cell death process that stabilizes cell numbers in tissues, can be independently induced by p53. METHODS In vivo gene transfer was used in isolated segments of balloon-injured rat carotid arteries. Genetically modified adenovirus encoding for wild-type p53 protein (AdWTp53) was applied at 8 x 10(10) plaque-forming units/mL. Control rats received either adenovirus null at the same concentration or balloon injury alone. Arteries were harvested at 24 and 48 hours after the procedure. Apoptosis was detected in tissue sections by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Specimens were graded either negative or positive less than 10%, 10% to 20%, 20% to 30%, or greater than 30% according to the number of apoptotic cells in the medial or intimal layer per high power field. Specimens were also subjected to DNA agarose gel electrophoresis and transmission electron microscopy. RESULTS With the TUNEL assay no apoptosis was visualized at 24 and 48 hours in the controls (n = 5 in each group), whereas in the AdWTp53 groups (n = 5 in each) all specimens presented apoptosis (P < .05, AdWTp53 vs controls). The average grade of apoptotic cells detected in the medial layer in the AdWTp53 groups was less than 10% to 20% at 24 hours and 20% to 30% at 48 hours. The DNA agarose gel electrophoresis failed to detect a DNA laddering pattern, characteristic of apoptosis. Electron microscopy revealed morphologic changes typical of apoptosis in the treated group, whereas specimens from control group did not reveal any apoptotic features. CONCLUSIONS At 48 hours after balloon injury alone, no apoptosis was observed in the vessel wall. However, when p53 gene was transferred, apoptosis was visualized in all specimens with greater intensity at 48 hours after injury. Promotion of apoptosis may play a key role in the mechanism by which p53 gene decreases intimal hyperplasia.

Protective effect of glycine in mesenteric ischemia and reperfusion injury in a rat model

PURPOSE Glycine has a protective effect in renal and skeletal muscle ischemia. The purpose of this study was to evaluate the effect of glycine in mesenteric ischemia and reperfusion injury in a rat model. METHODS Twenty-four anesthetized male Sprague-Dawley rats were subjected to 1 hour of mesenteric ischemia followed by 2 hours of reperfusion. Control animals received normal saline solution intravenously at 0.01 mL/g of body weight/h during ischemia and reperfusion. Treated animals received glycine at 0.5, 0.75, or 1.0 mg/g of body weight, dissolved in saline solution and infused at 0.01 mL/g/h for 2 hours. Animals were killed at the end of the experiment, and proximal, middle, and distal segments of the small bowel were isolated. Sections of the segments stained with hematoxylin-eosin were subjected to histologic examination (as per modified Chiu grading system) and morphometric analysis consisting of measurement of bowel wall, muscularis and mucosal thickness, epithelial coverage, and villar circumference. Isometric tension responses to electrical stimulation (10, 30, 50, 100 Hz), high doses of potassium (120 mmol/L), and carbachol (0.1, 0.5, 1.0, 5.0 micromol/L) were recorded in a multimuscle chamber. Statistical analysis was performed with unpaired t test and one-way analysis of variance. RESULTS The middle and distal segments of the small bowel in glycine-treated animals showed better histologic grade compared with saline solution-treated control rats (P <.05). At morphometric analysis, total thickness, mucosal thickness, and villar circumference ratio were well preserved in the middle and distal segments of the small bowel in the glycine-treated group (P <.05). No significant differences were observed in the proximal bowel segments between glycine-treated and control animals, because the proximal segment was not subjected to much ischemia. No differences were noted in percentage of epithelial coverage. Isometric tension responses evoked by electrical stimulation were greater (P <.05) in the middle and distal segments treated with glycine as compared with control segments. Carbachol-evoked contractions were stronger (P <.05) in the small bowel segments of animals treated with glycine. The responses evoked by 120 mmol/L of potassium were stronger in the distal segments of the small bowel in the glycine-treated group (P <.05). This cytoprotective effect of glycine was not dose-dependent. CONCLUSIONS Glycine improved mucosal viability in the ischemia and reperfusion injury rat model. Mucosal thickness and villous circumference ratio were reliable objective parameters for evaluation of intestinal ischemia injury. Glycine improved the contractile responses of the bowel segments also, probably by altering the physiologic mechanisms underlying force generation. Further studies are required to elucidate the mechanism of the cytoprotective action of glycine.

The value and limitations of magnetic resonance angiography of the circle of Willis in patients undergoing carotid endarterectomy.

Magnetic resonance angiography is a useful technique to determine the patency of the circle of Willis when compared with conventional four-vessel angiography. The purpose of this study is to determine whether the integrity of the circle of Willis, assessed by magnetic resonance angiography, provides adequate collateral cerebral circulation during carotid endarterectomy and correlates with internal carotid artery back pressure. Over a recent 20-month period, 35 patients were studied preoperatively with magnetic resonance angiography of the carotid bifurcations of the circle of Willis and the vertebrobasilar system. All patients underwent standard carotid endarterectomy with intraoperative measurement of internal carotid artery back pressure. Patients with an internal carotid artery back pressure < 50 mmHg had an intraluminal shunt placed. Deficiencies in branches of the circle of Willis, the carotid bifurcation and the vertebrobasilar system determined by magnetic resonance angiography were correlated with internal carotid artery back pressure using Fishers exact test. Only one patient had a completely intact circle of Willis. Eleven of 16 patients (69%) who had an internal carotid artery back pressure < 50 mmHg had an occluded A1 segment of the anterior cerebral artery combined with an occluded posterior communicating artery, whereas only five of 19 patients (26%) who had an internal carotid artery back pressure > 50 mmHg had similar findings (P < 0.03). Severity of occlusive disease of the contralateral internal carotid artery and the basilar artery did not independently predict internal carotid artery back pressure. An occluded anterior branch of the circle of Willis in combination with an occluded posterior branch of the circle of Willis is associated with an internal carotid artery back pressure < 50 mmHg. Although magnetic resonance angiography of the circle of Willis may provide valuable anatomic information, it is not sufficiently accurate to predict the need for carotid shunting and therefore its use cannot be justified on a routine basis.

Hemodynamic Instability following Carotid Endarterectomy Does Not Affect Early Discharge

Over the last few years, there has been increased emphasis on early discharge of patients following carotid endarterectomy in the United States. Recent studies have shown that short-stay hospitalization for carotid endarterectomy may be safe and cost-effective. However, this is not always possible because of reasons that are not clearly delineated. In order to optimize the early discharge of patients following carotid endarterectomy, an analysis of the causes of delayed discharges was performed in the present series. Since hemodynamic instability has been shown to be the most frequent complication following carotid endarterectomy, the authors investigated whether it was an important factor preventing early postoperative discharge. This study reviewed the data of 100 consecutive patients admitted for elective carotid endarterectomy. The incidence of post-carotid endarterectomy hemodynamic instability was 37% (n = 37), with hypertension occurring in 25 patients (68%) and hypotension occurring in 12 patients (32%). Hemodynamic instability tended to occur with the use of general anesthesia as compared with regional anesthesia. Hemodynamic instability did not correlate with pre-existent history of hypertension, nor with the type of drug used when general anesthesia was applied. All the patients were successfully treated either in the recovery room or in a monitored area. The average total length of stay was 1.65 days with 79% of the patients being discharged on the first postoperative day and 21% having delayed discharge ranging from 2 to 15 days (mean 4 days). The main reasons for delayed discharges were cardiac and urinary tract complications. Blood pressure instability accounted for only 2% of cases. Thus, these data show that hemodynamic instability does not significantly affect early discharge.

P53 Gene Transfer to the Injured Rat Carotid Artery Decreases Intimal Hyperplasia

Purpose We studied the effect of adenovirus-mediated gene transfer of p53 protein on the injured rat carotid artery to determine its ability to decrease the formation of intimal hyperplasia. Methods In vivo gene transfer was used in isolated segments of balloon injured rat carotid arteries. Genetically modified adenovirus encoding for wild-type p53 protein (AdWTp53) was applied in three different concentrations. Control rats received either adenovirus null (AdNull), 8 × 10 10 pfu/ml or M-199 medium solution (vehicle). Expression of p53 was determined 4 days after gene transfer by Western-blot. Intimal hyperplasia was assessed after 14 days by harvesting carotid arteries and determining the intima/media (I/M) ratio by cross-sectional area measurement. Simultaneously, immunohistochemical analysis was done to detect the presence of p53 on smooth muscle cell nuclei. Results p53 expression was confirmed by Western-blot. There was a significant reduction in intimal hyperplasia on all treated animals as compared with controls. The highest dose of AdWTp53 resulted in a near total arrest of intimal hyperplasia (mean of 97% reduction). A dose-response curve was observed. The immunohistochemical analysis was positive for the presence of p53 in rats infected with AdWTp53. The AdWTp53 groups have three different concentrations: #1, 8 × 10 10 pfu/ml; #2, 1.6 × 10 10 pfu/ml; and #3, 8 × 10 9 pfu/ml. Conclusions Adenovirus-mediated gene transfer of p53 protein significantly decreases the formation of intimal hyperplasia in the rat carotid injury model in a dose-response manner. This may represent a potential therapy for restenosis in humans.