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Background: Abdominal aortic aneurysms (AAAs) are frequently familial. The aim of this study was to compare the prevalence of AAA among the siblings of AAA patients with that in the spouses' siblings., Methods: The siblings of 375 AAA patients and the siblings of the spouses of the AAA patients were included in this study and offered ultrasonography screening for AAA. Participants were asked to complete a questionnaire to collect demographic and general health information. Statistical analysis was done with Fisher's exact test. Odds ratios and 95% confidence intervals were also calculated., Results: Abdominal ultrasonography examinations were done for 309 individuals. The results indicated that 11 (11.2%) of 98 brothers of AAA patients, 4 (2.7%) of 147 sisters, and none of the 64 siblings of the spouses of the AAA patients were found to have an AAA. Combining the information from the ultrasonography screening and medical records on already known cases of AAA in these families, altogether 29.0% (44/152) of the brothers of AAA patients, 11.1% (20/181) of the sisters of AAA patients, and 2.3% (2/88) of the siblings of the spouses had an AAA., Conclusion: There was a significant difference between the siblings of the AAA patients and those of the spouses both in the frequency of AAA detected by ultrasonography screening and in the overall prevalence of AAA. The overall prevalence of AAA in the siblings of AAA patients was about eight times that observed among the siblings of their spouses (19.2% vs 2.3%). These findings confirmed previous reports on high prevalence of AAA among siblings of AAA patients and emphasized the importance of an ultrasonography screening program for siblings of AAA patients.

Objective: This study investigated a large number of families in which at least two individuals were diagnosed with abdominal aortic aneurysms to identify the relationship of the affected relatives to the proband., Subjects and Methods: Families for the study were recruited through various vascular surgery centers in the United States, Finland, Belgium, Canada, the Netherlands, Sweden, and the United Kingdom and through our patient recruitment website (www.genetics.wayne.edu/ags)., Results: We identified 233 families with at least two individuals diagnosed with abdominal aortic aneurysms. The families originated from nine different nationalities, but all were white. There were 653 aneurysm patients in these families, with an average of 2.8 cases per family. Most of the families were small, with only two affected individuals. There were, however, six families with six, three with seven, and one with eight affected individuals. Most of the probands (82%) and the affected relatives (77%) were male, and the most common relationship to the proband was brother. Most of the families (72%) appeared to show autosomal recessive inheritance pattern, whereas in 58 families (25%), abdominal aortic aneurysms were inherited in autosomal dominant manner, and in eight families, the familial aggregation could be explained by autosomal dominant inheritance with incomplete penetrance. In the 66 families where abdominal aortic aneurysms were inherited in a dominant manner, 141 transmissions of the disease from one generation to another were identified, and the male-to-male, male-to-female, female-to-male, and female-to-female transmissions occurred in 46%, 11%, 32%, and 11%, respectively., Conclusion: Our study supports previous studies about familial aggregation of abdominal aortic aneurysms and suggests that first-degree family members, male relatives, in particular, are at increased risk. No single inheritance mode could explain the occurrence of abdominal aortic aneurysms in the 233 families studied here, suggesting that abdominal aortic aneursyms are a multifactorial disorder with multiple genetic and environmental risk factors.

Background: Human intravenous IgG (IVIG) containing specific antibodies protects neonatal rats from septic death. However, IVIG has immunosuppressive properties and clinical trials of IVIG in neonates at risk for sepsis have yielded conflicting results., Hypothesis: This study was designed to test the hypothesis that nonspecific antibodies in IVIG reduce survival in neonatal rats infected with Escherichia coli., Methods: Specific antibodies were adsorbed from IVIG with E. coli to produce IVIG/anti-E. coli-. After transthoracic administration of E. coli, survival was determined in neonatal rats injected intraperitoneally with phosphate-buffered saline, IVIG/anti-E. coli- (500 mg/kg) or IVIG containing anti-E. coli antibodies (IVIG/anti-E. coli+). Complement-mediated hemolytic activity of neonatal rat serum was quantified using sensitized sheep erythrocytes., Results: Compared with placebo, intraperitoneal IVIG/anti-E. coli- reduced neonatal survival after E. coli infection. In contrast, IVIG/anti-E. coli+ protected infected animals. Both IVIG/anti-E. coli- and IVIG/anti-E. coli+ impaired the complement-mediated hemolytic activity of neonatal rat serum., Conclusions: IVIG contained (1) nonspecific antibodies that reduced survival in neonatal rats infected with E. coli and (2) protective anti-E. coli antibodies that enhanced survival in neonatal rats infected with E. coli. We speculate that in clinical trials of IVIG to treat or prevent neonatal sepsis, inconsistent results may be caused, in part, by lot-to-lot variations in the ratio of immunosuppressive, nonspecific antibodies to protective, specific antibodies.

We report on a female infant with partial trisomy 9p (pter-->p13) and partial trisomy 14q (pter-->q22) resulting from a 3:1 segregation of a maternal reciprocal translocation (9;14)(p13;q22). Both trisomy 9p and partial trisomy 14q have been described as recognized phenotypes with characteristic patterns of anomalies. This patient appears to be the first reported with a partial duplication of both 9p and 14q resulting in an overlapping phenotype including minor facial anomalies, cleft palate, and hand-foot anomalies. However, the facial findings were more pronounced than commonly observed in cases with only one or the other duplicated chromosome regions, resulting in a distinctive appearance.

Aneurysms are characterized by dilation, i.e. expansion and thinning of all the arterial wall layers, which is accompanied by remodeling of the connective tissue. Genes involved in the regulation of tissue remodeling are therefore candidate genes. We analyzed TIMP1 and TIMP2 coding sequences in 12 individuals with abdominal aortic aneurysms (AAA), one individual with AAA and intracranial aneurysms (IA), four individuals with IA and two clinically unaffected individuals. We identified two nucleotide variants in both the TIMP1 and the TIMP2 coding sequences. All differences occurred in the third base positions of codons and were neutral polymorphisms. A significant difference was observed in the frequency of TIMP2 nt 573 polymorphism between 168 alleles from AAA patients and 102 control alleles.

Purpose: The goal of this randomized study was to determine whether combined general and epidural anaesthesia with postoperative epidural analgesia, compared with general anaesthesia and postoperative intravenous analgesia, reduced the incidence of perioperative myocardial ischaemia in patients undergoing elective aortic surgery., Method: Patients were randomly assigned to one of two groups. One group (EPI, n = 48) received combined general and epidural anaesthesia and postoperative epidural analgesia for 48 hrs. The other group (GA, n = 51) received general anaesthesia followed by postoperative intravenous analgesia. Anaesthetic goals were to maintain haemodynamic stability (+/- 20% of preoperative values), and a stroke volume > 1 ml.kg-1. A Holter monitor was attached to each patient the day before surgery. Leads 11, V2, and V5 were monitored. Myocardial ischaemia was defined as ST segment depression > 1 mm measured at 80 millisec beyond the J point or an elevation of 2 mm 60 millisec beyond the J point which lasted > 60 sec. An event that lasted > 60 sec but returned to the baseline for > 60 sec and then recurred, was counted as two separate events. The Holter tapes were reviewed by a cardiologist blind to the patient's group., Results: There were no demographic differences between the two groups. Myocardial ischaemia was common; it occurred in 55% of patients. In hospital, preoperative ischaemia was uncommon (GA = 3, EPI = 8). Intraoperative ischaemia was common (GA = 18, EPI = 25). Mesenteric traction produced the largest number of ischaemic (GA = 11, EPI = 11) events. Postoperative ischaemia was most common on the day of surgery. Termination of epidural analgesia produced a burst of ischaemia (60 events in 9 patients)., Conclusion: Combined general and epidural anaesthesia and postoperative epidural analgesia do not reduce the incidence of myocardial ischaemia or morbidity compared with general anaesthesia and postoperative intravenous analgesia.

Abdominal aortic aneurysm (AAA) meets the criteria as a possible target for early detection by screening or case-finding, although the effectiveness of such an intervention has not yet been demonstrated. The purpose of this study was to estimate the increase in cost-effectiveness that would result from selectively screening individuals based on their risk of AAA. Data from a hospital-based case-control study involving 78 men with AAA (unruptured) and 99 male controls were used to derive a risk function based on age, cigarette smoking, high blood pressure, history of heart disease, body mass index and serum high-density lipoprotein, using logistic regression analysis. For each of the control subjects (assumed to be a representative sample of the general population of elderly men), the risk of AAA was estimated and multiplied by the expectation of life to give a measure of the potential benefit of screening. The proportion of the total potential benefit that would be obtained by screening only those with a given level of risk was estimated, and this was related to the proportion of the population screened. In order to obtain 80% of the total potential benefit among men, we found that it would be necessary to examine 52% of the elderly male population if using a risk function based on age alone; 35% would have to be screened if age and smoking were included; and 17% would require screening if all the risk factors were included. Selective screening for AAA appears to be a promising strategy, but a prospective study is required to demonstrate that the predictions are valid.

There is evidence that the risk of abdominal aortic aneurysm (AAA) is greater in first-degree relatives of patients with the disorder than in the same age group of the general population. We conducted a 3-year study of siblings of AAA probands and siblings of a control group (cataract surgery patients) of the same age. Genetic information was obtained by interview from 126 probands and 100 controls; another family member was present at the interview. Medical records were obtained and further information verified before a sibling (over age 50) was assigned affected status. Of 427 siblings of probands, 19 (4.4%) had probable or definite AAA, compared with five (1.1%) of 451 siblings of controls. The lifetime cumulative risks of AAA at age 83 were 11.7% (SD 3.1) and 7.5% (4.1), respectively. The risk of AAA began at an earlier age and increased more rapidly for probands' siblings than for controls' siblings (p < 0.01, log-rank test). A risk comparison, based on the results of ultrasound screening of 54 geographically accessible siblings of probands and the 100 controls showed a similar pattern. Ten (19%) siblings of probands and eight (8%) controls had AAA on ultrasound (lifetime cumulative risk 60.8% [18.9] vs 14.9% [5.1], p = 0.01). These results show that familial factors influence the age of onset of AAA. We recommend routine ultrasound examination of siblings of patients with AAA.

Objective: To report the initial clinical experience with fibrinogen depletion using ancrod as prophylaxis and treatment for deep vein thrombosis and pulmonary embolism (DVT/PE) in patients with multiple trauma., Design: A series of cases, selected because of their extreme risk of DVT/PE or because of the appearance of thromboembolic complications despite prophylaxis using conventional methods., Setting: University teaching hospital., Patients: A referred sample comprising 30 patients with multiple blunt trauma. The mean injury severity score was 30. Most cases involved a combination of lower extremity, pelvic and chest injuries., Interventions: Fibrinogen was slowly depleted over 24 to 36 hours and the concentration maintained at 0.2 to 0.5 g/L thereafter. Ancrod was continued prophylactically (22 patients) or for established DVT/PE (8 patients) until the patients were mobilized or until there was no longer a contraindication to heparin, or until treatment with warfarin became practical., Main Outcome Measure: Monitoring for DVT by duplex ultrasonography or iodine-125-labelled-fibrinogen scanning, whichever could be applied., Results: Twenty patients were treated with ancrod for prophylaxis from the outset because it offered theoretic and practical benefits over other methods. No patient treated with ancrod for prophylaxis suffered a clinically significant DVT/PE. Patients in whom heparin prophylaxis failed and who experienced thromboembolic complications were effectively managed with ancrod. There were no deaths and no bleeding complications specifically due to the therapy., Conclusions: Slow depletion of fibrinogen with ancrod may provide a safe and effective means to prevent DVT/PE in multiple trauma patients or to treat DVT/PE when the risk of bleeding from heparin is great. This initial experience should be evaluated by a randomized controlled trial.

This article examines national and regional trends in mortality and morbidity due to abdominal aortic aneurysms from 1969 to 1991. Annual age-adjusted mortality and hospital separation rates were calculated for men and women aged 55 and older whose underlying cause of death was abdominal aortic aneurysm, or who were hospitalized with a primary diagnosis of abdominal aortic aneurysm. In recent decades, abdominal aortic aneurysm mortality rates remained stable, in contrast to substantial declines in mortality rates for cerebrovascular disease and cardiovascular disease. The pattern was similar for both sexes, although rates were four to five times higher among men than among women. In 1991, age-adjusted rates were around 31.0 per 100,000 men aged 55 and over and 8.5 per 100,000 women aged 55 and over. Over the 1969 to 1991 period, mortality rates in all regions tended to converge. Although mortality rates were stable, hospital separation rates for abdominal aortic aneurysms increased sharply, particularly for unruptured aneurysms. Screening programs have been able to detect asymptomatic abdominal aortic aneurysms, and surgical intervention can substantially reduce mortality. However, the costs and benefits of screening programs should be assessed. If current mortality rates persist, as the baby boom ages there will be an absolute increase in the number of deaths from abdominal aortic aneurysms.

Objective: To compare the outcome after aortoiliac endarterectomy and percutaneous transluminal angioplasty (PTA) of the aorta for localized stenosis of the lower abdominal aorta., Design: Chart review of patients treated over a 5-year period., Setting: A university centre., Patients: Sixteen women, all of whom were smokers; 5 had hyperlipidemia, 4 had evidence of coronary artery disease, 3 were hypertensive, and 1 was diabetic., Interventions: Aortoiliac endarterectomy (eight women) and PTA (eight women)., Main Outcome Measures: Ankle-brachial pressure index (ABI), degree of claudication and clinical outcome., Results: Angiography showed localized stenosis of the lower aorta in all patients, aortic hypoplasia in nine patients and associated common iliac disease in seven. None of the eight patients managed by aortoiliac endarterectomy had complications or died. All were free of claudication at a mean follow-up of 29 months and had durable improvement in their ABI: mean ABI preoperatively was 0.69 (standard deviation [SD] 0.1) and postoperatively was 1.06 (SD 0.07). Of the eight patients treated by PTA, only one had partial dilatation; another had a subintimal tear with worsening symptoms and a fall in ABI, requiring surgery within 18 months. The remaining six were symptom free after a mean follow-up of 13.4 months. Aortic PTA resulted in improvement of the ABI: mean ABI before PTA was 0.69 (SD 0.19) and after PTA was 1.06 (SD 0.15)., Conclusions: Endarterectomy is a safe and effective method of treating occlusive disease limited to the distal aorta. PTA appears to be less reliable. However, it is recommended as the initial treatment of choice in patients with angiographically suitable lesions because it is less invasive.

Objective: To assess how vascular surgeons define and manage asymptomatic abdominal aortic aneurysms (AAAs) 5.4 cm in diameter or smaller., Design: Descriptive survey., Setting: All provinces and territories of Canada., Participants: One hundred and ninety-one vascular surgeons., Interventions: A 12-item questionnaire sent in two mailings to all vascular surgeons who were members of the Canadian Society for Vascular Surgery., Main Outcome Measures: Definition and routine management of asymptomatic AAAs assessment of aneurysm size before elective surgery and basic personal data., Results: One hundred and sixty-seven (87%) vascular surgeons responded to the mailings; 149 (78%) completed the questionnaire. The majority of respondents were experienced (78%), academic (70%) vascular surgeons. AAAs were defined in any one of four ways. There was notable consistency regarding the size range in which vascular surgeons seriously considered elective surgical repair of small aneurysms., Conclusion: Standards need to be developed to define what constitutes a small AAA if meaningful research on small aneurysms is to be conducted.

Noninvasive testing is now routine for assessing vascular conditions. Many noninvasive tests are available for obtaining physiologic and anatomic information that is both precise and reproducible. This paper discusses noninvasive testing with plethysmography, Doppler ultrasonography, and duplex scanning for carotid artery occlusive disease, deep venous thrombosis, and peripheral arterial occlusive disease.

Background: The importance of cigarette smoking in the etiology of peripheral arterial occlusive disease is well known, but there have been few studies that have quantified this relationship., Methods: A case-control study design was used in which the case subjects were men with a history of claudication for at least 1 year and abnormal findings on noninvasive blood flow studies or on arteriography; control subjects were men attending the same hospital for conditions other than cancer, with no history of cancer or vascular disease and with a normal ankle-brachial index. Case and control subjects were interviewed by a trained nurse interviewer using a pilot-tested questionnaire. Current smoking status was confirmed by serum cotinine level estimation. Univariate odds ratios for smoking and other potential risk factors were calculated, and their significance was tested by comparison with the chi-squared distribution. Logistic regression analysis was used to adjust the effect of smoking for confounding variables, and the regression equation was used to estimate the proportion of disease attributable to smoking., Results: Of the patients approached, 94% of the eligible case subjects and 93% of the eligible control subjects agreed to participate. Recruitment ended with 102 cases of peripheral arterial occlusive disease and 99 controls. Most of the control subjects were attending clinics for other surgical specialties. Compared with men who had never smoked the relative risk was 7 for exsmokers and 16 for current smokers (p < 0.001). The relative risk increased directly with the lifetime number of cigarettes smoked, the chi-squared test for trend being highly significant (p < 0.001). Age, lipoprotein concentration, body mass index, and history of hypertension or heart disease were also significant risk factors., Conclusions: After adjustment for confounding variables the estimate of the fraction of disease attributable to smoking was 76%.

Although the intra-aortic balloon pump can be a lifesaving device, vascular complications are often associated with its use. Four hundred thirty-six patients underwent insertion of a balloon pump over a 14-year period. Indications for the balloon pump were intraoperative pump failure (42%), unstable angina (24%), preoperative prophylaxis (22%), preoperative shock (9%), and postoperative support (3%). Placement of the intra-aortic balloon pump was by percutaneous insertion in 66 per cent of patients, the remainder were placed by direct exposure of the vessel. Vascular complications occurred in 46 (10.6%) patients. Limb ischemia was seen in 40 of 46 of these patients. Other complications included bleeding in three patients, dissection in two patients, and infection in one patient. The effects on morbidity of sex, diabetes, site of cardiac catheterization, duration of counterpulsation, and the presence or absence of pulses on admission were determined. Only the absence of pedal pulses on admission correlated with an increased incidence of vascular complications (P = 0.04). Twenty four per cent of those with complications were diabetics, compared with 16 per cent of patients who received balloon pumps but had no complications. Surgical interventions in the ischemic limbs consisted of thrombectomy alone (28 of 40) or thrombectomy and vascular bypass (5 of 40). Four femorofemoral crossover grafts and one saphenous vein interposition graft were used. Five limbs were lost to amputation, or 1 per cent of the entire group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal studies have indicated that plasma tetrafluoroethylene (TFE) may be a better prosthetic material than expanded polytetrafluoroethylene (ePTFE) for arteriovenous access in patients who require hemodialysis because it combines the advantages of both Dacron and Teflon. A randomized clinical trial to compare the two materials was conducted between May 1987 and January 1989. Forty-four patients were enrolled, 22 in each group. The status of the grafts was monitored for at least 18 months. The patency rate for plasma TFE was 59% and for ePTFE was 64%. Kaplan-Meier analysis and Wilcoxon testing revealed no statistical differences between the two groups. Four grafts became infected, two in each group, and one aneurysm developed. Despite its theoretical advantages, plasma TFE was found to be similar to ePTFE as a graft material for hemodialysis.

Purpose: The purpose of this study was to compare the conduct and early results of infrainguinal vascular reconstructions with use of ancrod or heparin for anticoagulation., Methods: To test the hypothesis that ancrod was an effective alternative to heparin, 28 patients requiring infrainguinal bypass surgery were randomized to receive heparin during operation or ancrod before operation over a period of 12 hours to deplete circulating fibrinogen (0.2 to 0.5 gm/L)., Results: No clotting of blood within the grafts or native vessels was noted during the conduct of the surgical procedures in either group. No excessive bleeding was detected during operation in either group. The operative procedure, complication rate, and hospital course were also indistinguishable; patency at 1 month was also equal., Conclusion: Fibrinogen depletion with ancrod provides anticoagulation for the conduct of infrainguinal vascular reconstructions that is as effective as heparin. When heparin is contraindicated ancrod is an effective and safe alternative.

There have been several published definitions for abdominal aortic aneurysm (AAA), however, it is not known how different definitions affect what is reported. This paper presents an evaluation of three definitions taken from the literature on (a) aneurysm frequency, (b) prevalence rate and (c) prevalence ratio from an ongoing case-control study evaluating whether male siblings of patients with known AAA have a higher prevalence of aneurysms compared to a control group. Depending on the definition used, the frequency of AAA could vary from a low of five to a high of 23; the prevalence of AAA in siblings could range from 2.1 to 18.8. Changing definitions alters the prevalence ratio (risk of disease) in both magnitude and direction. On the one hand, male sibling of affected patients are at approximately one and a half times (1.6) greater risk of having an AAA compared to controls, whereas using a different definition they are at less than half the risk (0.3).

A retrospective case-control study was carried out to assess the importance of lymphatic fistulas that develop after vascular reconstruction and to determine the risk factors associated with them. The authors compared 35 patients who had lymphatic fistula after vascular reconstruction with 70 control patients, taken from the same database. They found a significant difference between the two groups only in age and indication for surgery: lymphatic fistulas were more likely to develop in older patients and in patients who underwent aortobifemoral bypass for limb salvage rather than for claudication (p less than 0.05).

The treatment of inflammatory aneurysms of the abdominal aorta presents a formidable challenge to the surgeon. The retroperitoneal inflammatory reaction obliterates normal tissue planes, limiting access to the infrarenal aorta. During a 70-month period 25 (6%) of 439 patients operated on for abdominal aortic aneurysms were found to have the inflammatory type. These patients were more likely to be symptomatic than patients with noninflammatory aneurysms and they were more likely to be male. Although surgical repair of the aneurysms required longer aortic occlusion time and more blood replacement, the outcome was similar to that for patients treated for noninflammatory aneurysms.

The measurement of left ventricular function by gated blood pool scanning and of myocardial perfusion by dipyridamole thallium imaging were compared in a prospective study of patients who had abdominal aortic aneurysm or aortoiliac occlusive disease to determine which measurement was the better predictor of postoperative cardiac complications. Sixty-six men and 19 women (mean age 67 years) underwent both tests before admission for surgery. Fifty-six had repair of an abdominal aortic aneurysm, and 29 had reconstruction for aortoiliac occlusive disease. In 17 patients the left ventricular ejection fraction was less than 50%. Dipyridamole thallium imaging was positive, showing redistribution, in 45 patients. Postoperative cardiac complications occurred in 33 patients. The sensitivity of dipyridamole thallium imaging (91%) was significantly (p less than 0.01) greater than that observed with gated blood pool scanning (27%). However, the specificity of gated blood pool scanning (85%) was similar to that of dipyridamole thallium imaging (71%). Diagnostic accuracy was greatest with dipyridamole thallium imaging (79% versus 62% [p less than 0.02]). Dipyridamole thallium imaging is superior to gated blood pool scanning for perioperative evaluation of vascular surgical patients.

Heparin-associated thrombocytopenia and thrombosis (HATT) is an infrequent occurrence but may have disastrous consequences. Continued therapy with heparin must be avoided and anticoagulation achieved by alternative means. Among the few alternatives to heparin in critically ill patients, the best is ancrod. Depletion of fibrinogen with ancrod results in anticoagulation comparable to therapy with heparin within 12 hours. In a small series, nine patients with HATT were treated with ancrod; one underwent angiographic assessment, angioplasty and subsequent vascular reconstruction. Ancrod therapy was not associated with bleeding complications. It appears to provide optimal therapy for patients suspected of having HATT.

Standard labelling methods using 111In-tropolonate in plasma resulted in lower labelling efficiency (LE) with pig granulocytes than with human cells. Addition of acid-citrate-dextrose (ACD) to cell-free plasma in a ratio of 1:10 tripled the LE to a value which was not significantly different from that obtained in saline. Under optimized conditions, LE was 67 +/- 2% (mean +/- SE) with pig granulocytes, which remained lower than that obtained with human cells but was adequate for nuclear imaging studies of granulocyte deposition in the pig.

There is increasing evidence for the involvement of inflammatory cells in the development of intimal hyperplasia. This study examines the effect of human neutrophils on the incorporation of [3H]-thymidine into acid precipitable materials (DNA) in cultured rabbit vascular smooth muscle cells. Co-culture of intact neutrophils and vascular smooth muscle cells caused [3H]-thymidine incorporation by these cells to increase 209 +/- 22% (mean +/- SEM) of control. Sonication of the neutrophils abolished this effect (117 +/- 10%). Neutrophil conditioned medium prepared in the presence or absence of fetal calf serum had a similar effect on [3H]-thymidine incorporation by vascular smooth muscle cells (204 +/- 20% and 172 +/- 17% respectively). Stimulation of neutrophils with either Concanavalin A or serum-activated zymosan failed to increase production of the factor(s). The neutrophil derived factor(s) prepared in minimal essential medium was partially stable at 56 degrees C, but inactivated by boiling. Dialysis (pore size 12,000-14,000) did not remove the factor(s). Cyclooxygenase inhibition with indomethacin did not inhibit production of the factor(s) by neutrophils, but indomethacin caused an increase in [3H]-thymidine incorporation by vascular smooth muscle cells (181 +/- 11%). Indomethacin together with intact neutrophils had an additive effect on [3H]-thymidine incorporation (273 +/- 42%) into cellular DNA. These data show that neutrophils produce a factor(s) that stimulates [3H]-thymidine incorporation into DNA by vascular smooth muscle cells and suggests that vascular smooth muscle proliferation and intimal hyperplasia may be initiated by neutrophils adherent to sites of endothelial injury.(ABSTRACT TRUNCATED AT 250 WORDS)

There is a growing appreciation of the magnitude of the problem of AAA in all Western countries. The large numbers of subjects needed to answer some of the questions, such as the natural history of small AAAs and risk factor analysis, requires that these studies be carried out by a multicentre group. The advantages of international collaboration, when possible, should ensure more uniform methods and definitions as well as more rapid recruitment of subjects. Granting agencies may find such an approach more attractive, and the results may be more relevant.

The vasomotor function of rabbit aorta was examined after deendothelialization with a Fogarty balloon catheter and during the subsequent development of intimal hyperplasia. Helical strips of injured lower abdominal aortic tissue showed an increase in norepinephrine-induced contraction when compared with control strips from normal upper abdominal aorta. This increase was 235% +/- 40% of control immediately after injury and 341% +/- 51% at 28 days after injury. Standardized dose-response curves demonstrated that the injured tissue was increasingly sensitive over time to norepinephrine and that this was more marked at physiologic levels of norepinephrine. Contraction was blocked by prazosin hydrochloride but not by yohimbine or propranolol. Furthermore, a single intramuscular dose of prazosin hydrochloride 2 hours before injury significantly (p = 0.001) reduced the maximal contraction and sensitivity. These results imply an increase in vasomotor reactivity after deendothelialization mediated through the alpha 1-adrenergic receptor. These functional changes are related to the pertinent morphologic observations.

The kinetics of the association of polymorphonuclear leukocytes (PMNs) with arterial balloon catheter-induced injury have been examined. An average of 6 X 10(7) PMNs were isolated from 20 ml of blood and labelled with 111In-oxine for reinfusion into the donor rabbit. The cells remained viable as demonstrated by both in vitro and in vivo tests of cell function. The abdominal aorta of rabbits was denuded of endothelium and immediately, 24 h, or 5 weeks later, exposed to autologous radiolabelled PMNs for 1 h. The presence of PMNs at sites of denudation was demonstrated by detection of the radioactive label and was confirmed by light and electron microscopy after 24 h, but not at 5 weeks. Immediately following denudation radioactivity was 2.44 +/- 0.33 times control (P = 0.006); 2.52 +/- 0.18 at 24 h (P = 0.005); and 1.88 +/- 0.32 times control at 5 weeks (P = 0.045). The presence of PMNs, or their products, 5 weeks after denudation suggests a more complex role of PMNs and possibly a direct involvement in the long term changes resulting from arterial balloon catheter injury.

To assess the prevalence of coexisting abdominal aortic aneurysm (AAA) within certain families, a retrospective review was carried out of patients who had undergone AAA repair over a 5-year period. Contact was made with 305 families (52%) and a positive history of an affected, first-degree relative was obtained in 34 (11%). A known AAA was reported to affect approximately 20% of siblings at risk when the proband had an affected parent or sibling. Siblings of patients with an affected first-degree relative represent a high-risk group that may benefit from a screening program for earlier detection and elective management of AAA.

A review of 59 popliteal aneurysms in 38 patients seen over 10 years revealed that 34 (58%) aneurysms were symptomatic. Symptoms included gangrene (15%), ischemia due to thrombosis (38%) and embolism (5%). Patients with unilateral aneurysms (45%) were a median of 7 years younger than those with bilateral lesions (55%). The latter group had more frequent manifestations of occlusive disease, which included previous myocardial infarction, coronary artery bypass grafting and stroke. They also had more concomitant aneurysms, those of the abdominal aorta and femoral and iliac arteries being the most common. Management consisted of bypass grafting in 34 limbs and immediate amputation in 9; 16 inoperable limbs remained viable. At last follow-up (median 32 months) or time of death, 30 of 34 grafts were patent. Four grafts occluded, one perioperatively and the others at 4, 5, and 32 months respectively, resulting in two amputations. The cumulative patency rate in the asymptomatic group was 94% compared with 81% in the symptomatic group. These data illustrate that patients with popliteal aneurysms may have associated vascular disease, the likelihood of which is increased when aneurysms are bilateral.

To rapidly start systemic anticoagulation there are few alternatives to heparin; those that may be used are often less effective and are impractical substitutes for various reasons. We report the cases of seven patients in whom anticoagulant therapy was begun with ancrod instead of heparin for one or more of the following reasons: (1) failure to achieve systemic anticoagulation in response to heparin (e.g., antithrombin III deficiency), (2) heparin-associated complications (e.g., thrombocytopenia, thrombosis, or both), and (3) combined anticoagulation and improved blood rheology considered to be potentially more beneficial than anticoagulation alone (e.g., massive thrombosis). In the cases reported, ancrod permitted systemic anticoagulation equal to that of heparin; this was achieved without bleeding complications. In contrast to streptokinase or urokinase, ancrod does not degrade preformed, fully cross-linked thrombin fibrin; consequently hemorrhagic complications are uncommon. Ancrod appears to be an appropriate alternative to heparin and may be preferable to it in certain circumstances.

Familial polyposis is an autosomal, dominantly inherited disorder. Usually less than 50% of siblings are affected because of incomplete penetrance by the responsible gene. The family described in this paper was unusual in that all seven siblings of one son had the disorder. The chances of this occurring, assuming complete penetrance, is 1 in 128. Moreover, several members of his family had Gardner's syndrome with associated extracolonic manifestations, including a rarely associated papillary carcinoma of the thyroid. There was no evidence of a cosanguineous marriage. Patients with familial polyposis are advised to adopt children, otherwise surveillance of their children must be lifelong, beginning at puberty.

Platelets are implicated both in acute thrombotic events and, through platelet-derived growth factor, in the development of intimal hyperplasia. We have investigated, in vivo, the influence of aspirin and dipyridamole on vascular smooth muscle cell proliferation and DNA synthesis following balloon catheter injury. Fifty-eight male, New Zealand white rabbits were divided equally into two groups; the test group was fed aspirin (14 mg/kg/day) and dipyridamole (9 mg/kg/day) from 2 days prior to surgery until sacrifice at 1, 2, 3, 4, 7, 14, or 28 days after injury. All animals were sacrificed 1 h after injection of [3H]thymidine and the smooth muscle cell DNA specific activity and total kinetic activity were determined. Intimal hyperplasia was measured by light microscopy and intimal nuclear proliferation was determined by counting nuclei per millimeter of internal elastic lamina. Nuclear proliferation was maximal at 14 days (25 +/- 1.2) but intimal hyperplasia was still increasing at 28 days. DNA specific activity after 24 hr (test: 4 +/- 2 dpm/micrograms DNA; control: 3.3 +/- 3 dpm/micrograms DNA) was similar to basal levels in uninjured rabbits. DNA synthesis peaked in both groups between the second and third day (test: 177 +/- 27 dpm/micrograms DNA; control: 185 +/- 39 dpm/micrograms DNA) and then declined slowly toward baseline values. There was no significant difference between treated and normal rabbits in either [3H]thymidine incorporation, nuclear proliferation, or development of intimal hyperplasia despite 90% inhibition of platelet aggregation and a significant reduction (78%) in [14C]serotonin release following collagen challenge (6 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS)