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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.

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.

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.

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.

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.

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.