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For the past three decades, the Healthy People initiative has represented an ambitious yet achievable health promotion and disease prevention agenda for the nation. The recently released fourth version-Healthy People 2020-builds on the foundations of prior iterations while newly embracing and elevating a comprehensive "social determinants" perspective. By clearly articulating a new overarching goal to "create social and physical environments that promote good health for all" and a new topic area dedicated to defining the social determinants of health approach, it breaks new ground. Specifically, the 2020 plan emphasizes the need to consider factors such as poverty, education, and numerous aspects of the social structure that not only influence the health of populations but also limit the ability of many to achieve health equity. Improving health is too multifaceted to be left to those working in the health sector alone. Using a social determinants approach can reframe the way the public, policy makers, and the private sector think about achieving and sustaining health. This article describes why such a social determinants approach can enhance our collective efforts to improve population health. This is achieved by defining the context for this new perspective, the process by which the Healthy People 2020 goals and objectives were developed, and the challenges and opportunities ahead. Adding this broad, social determinants perspective and vision for shared societal responsibility for change leaves Healthy People 2020 poised to promote a stronger legacy for a healthier nation and reaffirm a unity of purpose for the future.

To meet the dynamic and evolving challenges of public health in the 21st century, our society should foster the next generation of public health leaders. We offer a vision for doing so, by introducing prevention literacy and education from the earliest possible starting point and then broadening these concepts throughout the educational ladder. Making this societal commitment now to nurture such future leaders should make the country healthier by 2020 and beyond., (Published by Elsevier Inc.)

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.

Background: The development of colonic ischemia following repair of ruptured abdominal aortic aneurysm (AAA) is associated with significant morbidity and timely diagnosis is essential. The purpose of this study was to determine the efficacy of endoscopy in the diagnosis of colonic ischemia and in prediction of need for resection., Methods: Patients who underwent postoperative lower endoscopy after ruptured AAA from 1986 to 1995 were reviewed for endoscopic findings, clinical course, and patient outcome., Results: A total of 80 patients had ruptured AAA during the study period, of which 56 survived for longer than 24 h postoperatively. Flexible lower endoscopy was done in 18 patients (32%) on an average of 4.4 days following AAA repair (range 1-16). Indications for initial endoscopy included early or bloody stools in 12 (67%), hemodynamic instability or sepsis in eight (44%), and acidosis in four (22%). The extent of the examination was sigmoid or descending colon in 13, cecum in four, and transverse colon in one. Endoscopic findings were normal in four patients. Five examinations showed only areas of hemorrhagic mucosa. Absence of full-thickness ischemia was confirmed by clinical course or autopsy in these nine patients. Two examinations demonstrated full-thickness necrosis which was confirmed at subsequent laparotomy. In six examinations, ischemia was noted but judged to be limited to mucosa only. Absence of full-thickness disease was demonstrated by laparotomy in three and subsequent course in three. Eight patients (57%) with initial abnormal examinations underwent repeat endoscopy showing improved interval appearance in seven cases and progression to full-thickness ischemia in one patient., Conclusions: Flexible sigmoidoscopy reliably predicts full-thickness colonic ischemia following repair of ruptured aortic aneurysms. Patients with non-confluent ischemia limited to the mucosa can be safely followed by serial endoscopic examinations.

Background: In this study, the efficacy of composite sequential bypass is compared to that of standard in situ bypass, and to alternate prosthetic graft systems which have been used for the treatment of multilevel infrainguinal arterial occlusive disease in the absence of suitable autogenous vein., Patients and Methods: A retrospective review of graft patency and limb salvage included 197 patients undergoing 211 bypass procedures consisting of in situ femoral-tibial (IS; n = 119); composite sequential (CS; n = 35), prosthetic femoropopliteal with single (PFP-1; n = 30) or no vessel runoff (PFP-O; n = 9), and prosthetic femoral-tibial (PFT; n = 18) bypass., Results: By life-table analysis, IS bypass provided superior primary (P < 0.005) and secondary (P < 0.0005) patency over the other groups. CS bypass was similar to PFP-1, with a 2-two year primary patency of 35% and 44% (NS), respectively, and limb salvage rates of 60% and 80% (P = 0.01). PFP-O and PFT bypass procedures did considerably worse, with a 1-year patency of 19% and 22%, respectively, and associated limb salvage rates of 25% and 41% (NS)., Conclusions: Composite sequential bypass is an acceptable procedure for infrainguinal arterial reconstruction when absence of autogenous vein prevents either in situ or secondary vein graft bypass procedures.

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

Colonic ischemia is an often fatal complication of abdominal aortic aneurysm (AAA) repair. In elective AAA repair, patency of the inferior mesenteric artery (IMA) has been shown to be an important contributing factor. The purpose of this study was to determine which clinical and operative factors are important in the development of colonic ischemia in ruptured AAA repair. A retrospective review of all patients treated for ruptured AAA over a 7-year period was performed. Of 101 patients who were treated for ruptured AAA, 71 (70 per cent) survived for longer than 24 hours postoperatively, and these patients are the basis for this study. Colonic ischemia, primarily left sided, was a common perioperative complication (n = 24; 35 per cent) requiring colectomy in 11 patients (44 per cent). It carried a 44 per cent mortality compared to 20 per cent in patients without this complication (P = 0.07). Colonic ischemia occurred more frequently in patients with preoperative shock (P = 0.01) and a greater intraoperative blood loss (P = 0.003), but showed no correlation with patient age, co-morbid medical conditions, laboratory values, time to operation, or treatment of the IMA. Most patients with postoperative bowel ischemia were found to have chronic IMA occlusion, including 8 of the 11 patients requiring colectomy. Revascularization would not be feasible in this group. Revascularization of patent IMAs had little effect on outcome. Of the 17 patent IMAs, 9 were reimplanted and 5 (55 per cent) developed bowel ischemia, two of which required colectomy. Eight were ligated and 3 (38 per cent) developed bowel ischemia, one requiring colectomy. The presence of preoperative shock is the most important factor predicting the development of colonic ischemia following ruptured AAA. The incidence of ischemia is not altered by the presence of a patent IMA or with attempts at IMA revascularization. Colonic ischemia remains a significant source of morbidity and mortality in these patients.

Objective: To elucidate the time course and magnitude of hemodynamic and fibrinolytic changes associated with sequential gradient intermittent pneumatic compression (SGIPC)., Design: Two-phase, intervention and response investigation in normal volunteers., Materials and Methods: Subjects were assigned to control (phase I) or compression (phase II) groups. Serial blood samples were obtained via femoral venous catheters for tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), tPA-PAI-1 complex (tPA-PAI), and euglobulin lysis time (ELT) from all subjects and for fibrin degradation products (FbDP) and fibrinogen degradation products (FgDP) from phase II subjects. Duplex venous scanning was carried out on phase II subjects before and during SGIPC., Results: Catheter placement caused elevations in PAI-1 and tPA-PAI, which stabilized within 4 hours of catheter insertion. In phase II, SGIPC induced significant increases in FbDP, FgDP, and tPA-PAI and decreases in ELT and PAI-1, all of which quickly reverted to baseline on termination of compression. Femoral venous blood flow increased by more than 100% with SGIPC., Conclusions: Sequential gradient intermittent pneumatic compression induces prompt, but short-lived, alterations in both fibrinolytic and hemodynamic function. Noncontinuous SGIPC may result in suboptimal thromboembolic prophylaxis.

The initial stage of atherosclerotic plaque formation involves oxidation of the phosphatidyl-choline moiety of low density lipoprotein (LDL) and subsequent uptake by macrophages. Ongoing uptake in developing plaque also may involve oxidized LDL and would require an oxidizing environment in plaque lipids. Atherosclerotic plaque lipids from 12 patients undergoing peripheral vascular procedures were extracted in chloroform: methanol (2:1). This extract was applied to a 25 cm 5 micron silica HPLC column and eluted with a ternary gradient mobile phase utilizing a laser light scattering (ELSD) mass detector. Individual lipid fractions were then analyzed. Cholesterol, both free and esterified, was the most prominent lipid in plaque (104 +/- 74 mg/gm tissue. However, lipid peroxides were present in much higher concentrations (3.52 +/- 2.84 FU X 10(4)/mg phospholipid) and overall level (21.27 +/- 10.10 FU X 10(4)/gm plaque) in the phospholipid component (*p< 0.05). Phosphatidyl-choline (PC) accounted for 63% of the total phospholipid peroxides recovered (6.31 +/- 5.09 mg/gm plaque; *p<0.05). PC and phosphatidylinositol (PI) content were linearly related to lipid peroxide fluorescence (PC; r=0.696; p=0.01) (PI; r=0.809; p=0.001). Lipid peroxides in human atherosclerotic plaque are present primarily in the phospholipid component and phosphatidyl-choline forms the bulk of these peroxides. PC may play an important role in ongoing plaque lipid accumulation.

Background: Alternative methods for abdominal wall closure may be necessary after emergency laparotomy. The purpose of this study was to determine the morbidity and outcome of emergency fascial closure with polypropylene mesh., Methods: A retrospective review was performed of all patients undergoing emergency fascial closure with polypropylene mesh from January 1990 to March 1994., Results: Seventy patients were identified. Indications for mesh placement included visceral edema (40), infected/necrotic fascia (21), and planned reexploration (7). Enteric fistulas developed in five patients (7.1%). When omentum was interposed between intestine and mesh, the incidence of fistula was significantly reduced (0 of 51 vs 5 of 19, p < 0.01). Forty-two patients (60%) survived with wound closure, accomplished by skin flaps in 19 (45%), skin grafting in 11 (26%), and secondary healing in 6 (14%). The mesh was removed in six patients (14%). Complications of mesh extrusion and hernia occurred less often after skin flap closure compared with skin grafting or secondary healing (1 of 19 vs 9 of 17, p < 0.01). No mesh infection occurred., Conclusions: Polypropylene mesh placement is an effective alternative for abdominal closure after emergency laparotomy, even when intraabdominal sepsis is present. Fistulas associated with its use may be effectively eliminated by the interposition of omentum between bowel and mesh. Wound closure with full-thickness skin flaps is the preferred method for soft tissue coverage when mesh is used.

Increasing clinical and experimental evidence suggests a multifunctional role of calcium in determining the response of the arterial intima to atherogenic stimuli. In this study, an endothelial cell (EC)-smooth muscle cell (SMC) bilayer model of the arterial wall was used to investigate the effect of calcium manipulation on the sequestration of 125I-labeled LDL within the subendothelial space. Bilayer cell cultures were exposed to EGTA (0.25-2.0 mM), ionophore A23187 (5 x 10(-6) M), lanthanum chloride (0.1 mM), and trifluoperazine (TFP; 0.25 microM). The movement of 125I-labeled LDL (10 micrograms/ml) through the endothelial barrier was measured, as was the binding and cellular uptake of 125I-labeled LDL by each cell type. Extracellular Ca2+ chelation with EGTA and intracellular Ca2+ mobilization with A23187 both increased EC permeability to LDL (P < 0.05; P = 0.0001, respectively), while not significantly affecting EC binding or uptake of lipoprotein. Conversely, these agents increased SMC uptake of LDL (P < 10(-7); P < 10(-8), respectively). Calcium blockade with lanthanum chloride had the opposite effect, reducing EC permeability (P = 0.011) and SMC uptake (P < 10(-5)), while increasing EC uptake (P = 0.016). TFP, a calmodulin inhibitor, had an effect similar to A23187, although reducing SMC uptake of LDL (P = 0.015). Alteration of the calcium gradient across the plasma membrane appears to influence EC permeability. This effect may be stabilized by Ca2+ blockade or calmodulin regulation of cytoplasmic Ca2+. Additional anti-atherogenic effects of calcium blockade may include a reduction in SMC uptake by the SMC.

Poor outcomes following transcranial gunshot wounds (TC-GSW) and the perception of significant financial loss have led some institutions to adopt a fatalistic attitude towards these patients. This study was undertaken to define those factors predictive of mortality following TC-GSW as well as to determine the costs and benefits associated with providing care to these individuals. We reviewed the medical records of 57 TC-GSW patients seen at our Level I Trauma Center between January 1990 and December 1992. Overall mortality was 75 percent, and was statistically associated with an admission Glasgow Coma Score of 4 or less, a respiratory rate of less than 10, and self-inflicted wounds. Complete financial information was available for 37 of the 57 patients. Reimbursements for this group were $306,156 and exceeded costs by $62,257. Organ donation efforts were successful in 44.2 per cent of the nonsurvivors (19/43), yielding 60 organs and 29 tissues for transplantation. Nonsurvivors who became organ donors were clinically and demographically indistinguishable from those in whom organs/tissues could not be retrieved. Despite the poor outcome following TC-GSW, vigorous resuscitation and stabilization is justified in all patients, in that nearly one half of nonsurvivors will become organ and/or tissue donors. Concerns regarding excessive monetary looses by treating facilities are unfounded.

Elderly patients with abdominal aortic aneurysms (AAA) may be deemed inoperable due to the presence of comorbid conditions. Presentation of these patients with acute rupture can then result in difficult ethical decisions regarding surgical treatment. Over six years, 80 patients were treated emergently for ruptured AAA. Of these patients, 26 (32.5%) had known aneurysms. This study was performed to determine outcome and factors affecting mortality in patients with known AAAs. There were no significant differences between known and unknown AAA groups with regard to operative risk. In the overall group (n = 80), patient delay in seeking treatment averaged 20.4 hours with a trend towards shorter times in those with known AAAs (13.8 hours) compared with the unknown group (23.6 hours; p = 0.09). Medical transport delay, however, was significantly shorter for patients with known AAA (124 minutes versus 230 minutes; p = 0.04). Overall mortality was 56 per cent (n = 45). Those patients with known AAAs had a higher mortality (69%; n = 18) than those with unknown AAAs (50%, n = 27) but this was not statistically significant (P = 0.10). In patients with known AAAs, operative death was related to patient delay, with an average delay in seeking medical advice of 21.3 hours in nonsurvivors compared with 8.6 hours in survivors (P = 0.04). No other risk or demographic factors correlated with mortality. Despite a known AAA, significant delay in seeking medical advice occurred, and this delay resulted in decreased survival. Patient education is imperative if nonoperative treatment is chosen.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: The authors determined the risk factors of mortality in patients with necrotizing soft-tissue infections (NSTIs) and examined the incidence and mortality from NSTI secondary to Streptococcus pyogenes., Methods: All patients with NSTIs who were treated between January 1989 and June 1994 were analyzed for presentation, etiology, factors important in pathogenesis and treatment, and mortality., Results: Sixty-five patients were identified with NSTIs secondary to postoperative wound complications (18), trauma (15), cutaneous disease (15), idiopathic causes (10), perirectal abscesses (3), strangulated hernias (2), and subcutaneous injections (2). Necrotizing soft-tissue infections were polymicrobial in 45 patients (69%). S. pyogenes was isolated in only 17% of the NSTIs, but accounted for 53% of monomicrobial infections. Eight of ten idiopathic infections were caused by a single bacterium (p = 0.0005), whereas 82% of postoperative infections were polymicrobial. An average of 3.3 operative debridements per patient and amputation in 12 patients were necessary to control infection. The overall mortality was 29%; mortality from S. pyogenes infection was only 18%. The average time from admission to operation was 90 hours in nonsurvivors versus 25 hours in survivors (p = 0.0002). Other risk factors previously associated with the development of NSTIs did not affect mortality., Conclusions: Early debridement of NSTI was associated with a significant decrease in mortality. S. pyogenes infection was the most common cause of monomicrobial NSTI, but was not associated with an increased mortality.

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.

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 medical records of 91 patients who underwent thyroidectomy from 1990 to 1993 were reviewed to evaluate airway management and operative morbidity in patients with marked thyroid enlargement. Twenty-nine patients with marked thyroid enlargement were identified: 13 unilateral, defined by a weight of > or = 40 g (mean 122 g, range 41-380 g), and 16 bilateral, defined by a weight of > or = 80 g (mean 160 g, range 82-404 g). Twenty-five patients had compressive symptomatology, 18 had tracheal narrowing and/or displacement, 19 had substernal extension, and one had superior vena cava syndrome. Unilateral vocal cord dysfunction was present in two of three patients with carcinoma and one of 26 patients with benign disease (P = 0.03). Pathology consisted of nodular goiter (11), adenoma (5), carcinoma (3), Grave's disease (5), and toxic multinodular goiter (5). All patients had an uncomplicated endotracheal intubation without the use of a fiberoptic bronchoscope as predicted on the basis of preoperative laryngoscopic findings. Ease of intubation was unrelated to the extent of abnormality seen on imaging studies of the neck. Thyroidectomy alone was effective in relieving compressive symptoms with no incidence of nerve injury, permanent hypoparathyroidism, or tracheomalacia. Six (21%) of 29 patients had temporary hypocalcemia compared to eight (13%) of 62 patients with lesser thyroid enlargement (P = 0.36). One patient with an unresectable follicular carcinoma died from aspiration pneumonia three weeks following tracheostomy placement. Marked thyroid enlargement and upper airway compression is predominantly caused by benign disease; however, when there is associated recurrent laryngeal nerve dysfunction, carcinoma is more common.(ABSTRACT TRUNCATED AT 250 WORDS)

Early recognition and treatment of necrotizing fasciitis (NF) is essential for survival. The diagnosis of primary or idiopathic NF may be particularly challenging because it occurs in the absence of a known causative factor or portal of entry for bacteria. Patients with NF treated between 1989 and 1993 were reviewed to determine the incidence, clinical features, bacteriology, and results of treatment in patients with idiopathic NF. Idiopathic NF occurred in nine (18%) of 51 patients, five men and four women, ranging in age from 21 to 67 years. Associated conditions included diabetes mellitus (4), alcoholism (3), remote infection (3), and pregnancy (2). NF affected the lower extremity in eight and the perineum in one patient. Pain and tenderness occurred in all patients, soft tissue gas was recognized in two, and the presence of erythema and edema was variable. Idiopathic NF was monomicrobial in seven (78%) patients, compared to 21 per cent of patients with secondary NF (P = 0.003). S. pyogenes was the causative organism in five of seven monomicrobial infections. Time from admission to operation was significantly longer (62.3 +/- 54.8 hours) in patients with idiopathic NF compared to patients with secondary NF (17.0 +/- 16.6 hours) (P = 0.001). Treatment included operative debridement (means = 3.3) and limb amputation (n = 1) to control infection. Three patients (33%) with idiopathic NF died. Primary or idiopathic NF is principally a monomicrobial infection usually caused by S. pyogenes that most commonly occurs in the extremities. Mortality is high but is comparable to secondary NF. It is important to recognize that NF may occur spontaneously, and it should be suspected in patients with unexplained soft tissue pain and tenderness.

Second messenger signaling has been shown to regulate a variety of cellular functions in response to external stimuli. The following study was performed to determine the potential role of second messengers on influencing lipoprotein uptake by the arterial wall. An aortic endothelial cell (EC)-smooth muscle cell (SMC) bilayer was preexposed to various mediators of the cyclic AMP and inositol phosphate pathways for 30 min. The permeability, binding, and cellular uptake of 125I-labeled low-density lipoprotein (LDL) (10 micrograms/ml) added to the upper well media of the bilayer were then measured for each cell type after a 3-h incubation period. Forskolin (100 microM), an activator of adenylate cyclase, resulted in an increase in all measured parameters. 8-Br-cAMP (30 microM), a cAMP analogue, showed a similar effect on EC permeability (P < 0.00005) while galanin (0.1 mg/ml), an adenylate cyclase inhibitor, had no effect. GTP-binding protein inhibition with pertussis toxin (10 mg/ml) led to a marked reduction in SMC uptake (P < 10(-7)) without affecting membrane binding. Protein kinase C activation with phorbol myristate acetate (0.1 mg/ml) also increased EC permeability to LDL but, unlike forskolin, had no effect on LDL binding. This effect was further potentiated by calcium ionophore A23187 (5 x 10(-6) M), indicating a contributing role of intracellular calcium. These results would suggest that LDL uptake can be influenced by several second messenger systems, and that EC and SMC may respond differently to these intracellular signals. Second messenger regulation may allow changes in lipoprotein uptake by the arterial wall in response to external stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose: Calcium channel blockade has been shown to inhibit experimental atherosclerosis in cholesterol-fed animals, and early clinical trials suggest its benefit in human subjects as well., Methods: To determine the effect of the calcium channel blocker nifedipine on lipid and monocyte infiltration of the subendothelial space, an endothelial cell (EC)-smooth muscle cell (SMC) bilayer model of the arterial wall was incubated for 18 hours with nifedipine (0.1 micrograms/ml). Iodine 125-labeled low-density lipoprotein (125I-LDL) (10 micrograms protein/ml) was then added to the upper-well medium., Results: After a 3-hour incubation period, nifedipine-treated bilayers showed an increased permeability to LDL (p < 10(-7). Nifedipine had no effect on the membrane binding or cellular uptake of LDL by the EC but did increase SMC binding and uptake (p < 0.0005). U937 monocytes were found to incorporate 125I-LDL in a concentration-dependent fashion, without saturation to 25 micrograms/ml, the highest concentration studied. Nifedipine increased monocyte uptake of LDL (10 micrograms/ml; p < 0.003 but reduced monocyte movement through the EC barrier (p < 10(-7). A study of the selective preincubation of each cell type (EC, SMC, and monocyte) with nifedipine indicated that this reduction was likely the result of a direct effect on the monocyte., Conclusions: Given the potential cytotoxic effects of the monocyte within the subendothelial space, nifedipine-induced inhibition of monocyte infiltration and enhancement of lipoprotein uptake by the SMC may be protective.

Lipid peroxidation products and the fatty acid composition of phospholipids were studied in the hearts of rats chronically consuming ethanol supplemented with large amounts of vitamin E. Ethanol representing 36% of the total calories was ingested for 7 weeks in a modified Lieber-DeCarli liquid diet that contained vitamin E at 30 IU/L in the control or 172 IU/L in the supplemental dietary group. Ethanol and/or vitamin E did not change the absolute content (micrograms per mg of phospholipids) of the main fatty acids (C18:0, C18:2, and C20:4) of heart phospholipids but increased the amount of the minor C20-C22 fatty acids. Cardiac phospholipid levels increased in rats chronically consuming excess vitamin E and/or alcohol. Chronic ethanol consumption caused elevations of the relative content (percent of total fatty acids) of tri-, tetra-, and hexaenoic acids and peroxidizability index (PI) of the cardiac phospholipids. Supplementation with vitamin E blocked this ethanol-induced shift in the fatty acid profile toward unsaturation and decreased the PI. Ethanol enhanced accumulation of vitamin E in heart tissue by 30% irrespective of the vitamin E content in the diet. Enrichment of the diet with vitamin E coincided with the low levels of fluorescent products in heart lipids. A positive correlation (r = 0.36; p = 2%) was found between vitamin E and diene conjugates in the heart cells. Thus, vitamin E has a stabilizing effect on heart phospholipids by preventing changes in their fatty acid composition and peroxidative deterioration.

Thrombin, a mediator of thrombosis, has been shown to directly alter the function of vascular cells. We studied the effect of thrombin on low-density lipoprotein permeability and uptake by an arterial endothelial cell-smooth muscle cell bilayer to determine its potential role in atherogenesis. Confluent cell bilayers were incubated in media containing thrombin (10 or 50 units/ml) for a period of 24 hours to 9 days. Iodine 125 (125I)-LDL (10 micrograms protein/ml) was then added to the media, and after a 3-hour incubation, 125I-LDL transit through the endothelial cell layer as well as membrane binding and uptake by each cell type were measured. The lower concentration of thrombin caused a delayed increase in both the permeability (p less than 0.0001) and uptake (p less than 0.05) of LDL, but had no effect on membrane binding of the lipoprotein. The higher thrombin concentration led to an immediate increase in endothelial cell permeability to LDL (p less than 10(-7)) and a significant reduction in both cellular uptake (p less than 10(-7)) and membrane binding (p less than 0.0005). In contrast, smooth muscle cell binding and uptake were unaffected at the lower concentration of thrombin. At the higher concentration, smooth muscle cell uptake of LDL was increased (p less than 10(-7)) disproportionately to a more limited increase in membrane binding (p less than 0.05). Endothelial DNA content, reflecting cell number, was increased at 10 units/ml thrombin (p less than 0.001) but markedly reduced at 50 units/ml thrombin (p less than 0.0005), whereas smooth muscle cell DNA content remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

In the past 3 years at our institution 130 patients have undergone cardiac transplantation for ischemic cardiomyopathy in 49 (38%), idiopathic cardiomyopathy in 42 (32%), viral cardiomyopathy in 9 (6.9%), pulmonary hypertension in 8 (6%), and graft atherosclerosis in 2 (1.5%). Routine preoperative abdominal ultrasonography was performed on 98 (75%) of these patients with specific visualization of the abdominal aorta in 93 (95%). Abdominal aortic aneurysms (all infrarenal) were found before operation in four patients and only in the subgroup undergoing transplantation for ischemic heart disease (10.5%). They measured 3.4, 4.5, 3.6, and 3.8 cm before transplantation. Periodic evaluation by ultrasonography was carried out after transplantation during the 3-year period of this study. One aneurysm that was initially 3.6 cm increased to 4.0 cm and ruptured 2 months after transplantation. The patient died despite emergent surgery. Aneurysms in three patients who demonstrated rapid aneurysm expansion after transplantation were successfully repaired at 5, 20, and 33 months after transplantation when the lesions reached 5.5, 5.9, and 4.8 cm. A fifth patient with an initially normal (1.5 cm) aorta developed a symptomatic aneurysm of 4.1 cm, which was repaired uneventfully. The average expansion rate of these aneurysms after transplantation was 0.74 +/- 0.15 cm/year. This experience suggests that aneurysms are limited to patients undergoing transplantation for ischemic heart disease. Ultrasound examination may be appropriate for preoperative screening. Careful aortic surveillance after transplantation is important in patients having transplantation for ischemic cardiomyopathy because of the apparent rapid expansion rate compared to aneurysms in the population not receiving transplants.

Intraarterial urokinase (IAUK) was administered to 33 patients on 40 occasions for the treatment of acute extremity ischemia and long-term patency was assessed. Lysis was successful in 39 of the 40 cases (95%). Occlusive thrombus was cleared in 12 of 13 patients with native artery occlusion (7 complete, 5 partial), 8 of 9 with autologous vein grafts (5 complete, 3 partial), and in all 18 patients with synthetic grafts (17 complete, 1 partial). The primary cumulative patency following successful IAUK was 100% for native arteries and 47% for synthetic grafts at 12 months, and 23% for autologous grafts at 9 months. The difference in rethrombosis rate between autologous vein (67%) and native artery (0%) was significant (p = 0.02) as was the difference between infrainguinal prosthetic grafts (63%) and native artery (p = 0.025). IAUK is most effective for the treatment of native artery occlusion, but is significantly less effective for thrombosed infrainguinal autologous vein or synthetic grafts due to the likelihood of reocclusion, despite the high immediate success rate. For autologous vein grafts, lysis is frequently incomplete and patency rapidly deteriorates regardless of adjunctive therapy to relieve the underlying obstruction.

A failing femorotibial in situ saphenous vein bypass graft was found by angioscopic examination to be lined with white thrombus and was successfully treated by intraoperative lytic therapy rather than by thrombectomy with a balloon catheter. The platelet-fibrin debris was completely cleared by 250,000 units of urokinase. There were no bleeding complications and the potential for mechanical damage to the venous endothelium was prevented. The in vivo angioscopic observations of fibrinolysis are described.

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.

We evaluated the effects of alcohol ingestion on aortic lipid concentrations in 15 pair-fed Sprague-Dawley rats divided into three groups of five animals each. Control rats were fed a liquid diet, with 36% of their energy provided by maltose-dextrin for 28 days, and the remaining two groups of rats were fed an equivalent proportion of their energy as alcohol for 28 days or 18 months. Alcohol-fed rats exhaled significantly greater quantities of ethane than did controls at 28 days and 18 months. Serum cholesterol levels increased by 40% and triglyceride levels increased by 80%, but phospholipid levels remained unchanged in alcohol-fed rats compared with controls. Aortic concentrations of cholesterol and phospholipids increased twofold and threefold, respectively, in alcohol-fed rats, with a corresponding alteration of the cholesterol-phospholipid ratio at both time intervals. Tissue triglyceride levels were only elevated at 28 days, and no differences in aortic lipid peroxide levels were detected between alcohol-fed rats and controls. The results of the study indicate that alcohol ingestion increases aortic cholesterol, phospholipid, and triglyceride levels at 28 days and cholesterol and phospholipid but not triglyceride levels at 18 months. The mechanisms underlying the accumulation of lipids in aortic tissue need further elucidation.

Spontaneous bile duct rupture occurred in a 23-year-old who required emergency Cesarean section for fetal distress. This condition has not been reported in association with pregnancy. Only forty cases of spontaneous bile duct perforation in adults have been previously reported. Seventy percent of these perforations were related to biliary calculi. Sites of perforation were evenly distributed between common hepatic duct and common bile duct. Recommended treatment includes cholecystectomy, common bile duct exploration, T-tube placement, and Roux-En-Y ductal anastomosis if disruption is extensive.

Lipid peroxidation may play a significant role in the initiation and progression of atherosclerotic plaque. Freshly harvested normal and atherosclerotic human aortic tissue, coronary arteries and explanted vein grafts were snap frozen at -70 degrees C. Folch reagent (chloroform-methanol 2:1, v/v) was used to extract lipids from the homogenates. These extracts were assayed for cholesterol, phospholipid and triglyceride content. Lipid peroxide complexes in vessels were measured fluorometrically. Atherosclerotic plaque from patients with aortic aneurysmal and occlusive disease and coronary artery disease contained significantly greater amounts of cholesterol (15.54 +/- 9.71 vs 3.39 +/- 1.14 mg/g tissue) than controls (p less than 0.01). Lipid peroxide fluorochromes were similarly elevated in all atherosclerotic tissue (4.159 +/- 1.065 vs 3.087 +/- 0.497 fluoro units/g tissue) compared to control (p less than 0.01) with significant elevations in saphenous vein grafts and occlusive aortic disease. Although lipid peroxidation and lipid accumulation occur in close association in atherosclerotic plaque, the role of lipid peroxides in the pathogenesis of atherosclerosis remains to be determined.

An arbitrary delay of at least 6 weeks before performing carotid endarterectomy after acute stroke has been recommended based on anecdotal reports. This prolonged interval may increase the danger of recurrent neurologic deficit before surgery. From September 1978 to September 1988, carotid endarterectomy was performed on 140 patients at variable intervals after stroke. Eleven patients had temporary stroke, which left 129 patients with neurologic symptoms that persisted for 3 weeks or had a cortical infarct on CT scanning. A prospective therapeutic protocol was applied to 82 patients admitted with acute stroke. They were observed until neurologic recovery reached a plateau, based on clinical observation by a neurologist, before performing angiography and carotid endarterectomy (group I). Forty-seven patients were not seen until after recovery from stroke was established (group II). At initial presentation, the severity of neurologic deficit was classified as mild, moderate, or severe in 31%, 58%, and 11%, respectively. Recovery before operation was registered as complete in 11%, mild residual in 66%, moderate residual in 21%, and severe residual in 2%. Group I patients (n = 82, 64%) were operated on within 6 weeks of stroke and group II (n = 47, 36%) were operated on at varying times after 6 weeks. No significant difference was found in the incidence of cerebrovascular events (1.2% vs 4.2%) and deaths (1.3% vs 2.1%) between groups I and II with respect to the timing of carotid endarterectomy, and no significant difference was found between patients operated on at 2, 4, 6, or more than 6 weeks after stroke.(ABSTRACT TRUNCATED AT 250 WORDS)

The ideal vascular graft has not yet been developed. However, in the aortic position, excellent results can be obtained using a variety of currently available grafts, which offer similar patency rates and durability. Therefore, graft selection depends on other considerations, such as the ease of handling and preclotting requirements.

Emergency Department tracheostomy is performed in the rare instances of extensive laryngeal trauma in the adult and emergent airway access in the infant. This article reviews indications, anatomy, technique, and complications of this challenging life-saving procedure.

Innominate vein thrombosis as a result of previous hemodialysis catheter placement occurred in a patient with a functioning radial-cephalic fistula, resulting in massive edema with bleb formation. Diagnosis was confirmed by magnetic resonance imaging and the complication was successfully managed by subclavian vein-superior vena cava bypass. This experience suggests the need to consider the possibility of proximal vein occlusion in selecting arteriovenous fistula sites and, rather than abandoning the fistula, allowing it to serve to protect patency of a proximal bypass.

Antiplatelet aggregators such as sulfinpyrazone (10 mg/kg), ticlopidine (200 mg/kg), and pyridine (0.1 mg/kg) significantly inhibited the degree of gastric ulceration in Sprague-Dawley rats subjected to cold restraint stress. The inhibition of platelet aggregation and that of microthrombus formation were evident in rats given antiplatelet aggregating drugs and exposed to cold stress. Therefore, platelet aggregation does play an important role in stress ulcer formation, and drugs which inhibit this aggregation should be given greater attention as to possible clinical application for treatment of stress ulcers.

Thirty-two diabetic patients with foot ulcers were evaluated. Twenty-five patients had foot radiographs, technetium-99m bone scans, and wound and bone cultures; the remaining seven patients had all the studies except bone scanning. Bone changes compatible with osteitis were present on 15 of 32 foot radiographs (47 percent) and on 16 of 25 bone scans (64 percent). Bacterial growth was present in 27 of 32 wounds (84 percent) and 23 of 32 bone cultures (72 percent). Twelve of 23 patients (52 percent) with positive bone cultures had evidence of bone destruction and periosteal reaction on radiographs. The remaining 11 of 23 patients (48 percent) without radiographic signs of osteitis had bacterial growth from their bone cultures. Bone scans were positive in 12 of 18 patients (67 percent) with positive bone cultures and negative in 6 of 18 positive bone cultures (33 percent). We conclude that neither foot radiographs, technetium-99m bone scans, nor wound cultures should be used as the sole criterion for determining the use of antibiotic therapy or amputation in diabetic patients with foot ulcers.

The effect of pyridine in the prevention of cold restraint-induced stress ulcers in rats was investigated. After fasting, rats were administered the appropriate dosage of pyridine and were promptly placed into stress cages for cold room stress. The rats were sacrificed and bleeding, ulceration and vascular patency were examined. At doses of 0.01 mg/kg and 0.20 mg/kg, pyridine significantly decreased the amount of gastric hemorrhage and ulceration (p less than 0.01), as compared with the controls. In addition, microvascular dye, injected after stress, revealed perfused mucosal capillaries in the pyridine group, and occlusion of mucosal capillaries in the control group. These results suggest that the antiplatelet effect of pyridine reduced thrombus formation in the mucosal capillaries with subsequent reduction in mucosal ulceration.

Aortobifemoral bypass (ABF) is the preferred operation for patients with bilateral aortoiliac occlusive disease, but for those with unilateral occlusion without significant stenosis of the contralateral iliac artery, alternative reconstructions, such as femorofemoral (FF) or iliofemoral (IF) bypass have been advocated. We compared the surgical outcome in 96 such patients after ABF (n = 32), FF (n = 47), or IF (n = 17) bypasses, with biplane arteriography and noninvasive laboratory testing used to assess the contralateral iliac artery and runoff status, in particular, patency of the superficial femoral artery (SFA). Graft patencies were assessed by noninvasive criteria and analyzed by the life-table method. The only death occurred after ABF bypass (3.1%). Primary patency rates at 1, 3, and 5 years with an open SFA were 100%, 89% and 89%, respectively, for ABF; 92%, 92%, and 92% for FF; and 71%, 71%, and 36% for IF. When the SFA was occluded, the primary patency rates at 1, 3, and 5 years were 100%, 100%, and 72%, respectively, for ABF; 72%, 53%, and 35% for FF; and 56%, 56%, and 56% for IF bypasses. There were no later occlusions on the contralateral ("good") side after ABF. Significant progression of atherosclerosis in donor iliac artery was observed in 6% of both FF and IF bypasses. We conclude that ABF is the preferred operation for extensive iliac artery occlusive disease that is hemodynamically significant only on the symptomatic side unless specifically contraindicated by prohibitive risk or abdominal disease. This is particularly true in the face of SFA occlusion.