Nonspecific human IgG reduces survival in neonatal rats infected with Escherichia coli.

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.

Analysis of coding sequences for tissue inhibitor of metalloproteinases 1 (TIMP1) and 2 (TIMP2) in patients with aneurysms.

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.

Case of partial trisomy 9p and partial trisomy 14q resulting from a maternal translocation: overlapping manifestations of characteristic phenotypes.

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.

Perioperative ischaemia in aortic surgery: combined epidural/general anaesthesia and epidural analgesia vs general anaesthesia and i.v. analgesia.

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.

Selective screening for abdominal aortic aneurysm.

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.

Sibling risks of abdominal aortic aneurysm.

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.

Ancrod as prophylaxis or treatment for thromboembolism in patients with multiple trauma.

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.

Trends in mortality and hospital morbidity due to abdominal aortic aneurysms.

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.

Endarterectomy versus angioplasty in the treatment of localized stenosis of the abdominal aorta.

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.

Definition and management of abdominal aortic aneurysms: results from a Canadian survey.

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 blood flow tests in vascular disease.

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.

Cigarette smoking 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%.

Vascular complications of the intra-aortic balloon pump: an analysis of 436 patients.

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)

A comparison between expanded polytetrafluoroethylene and plasma tetrafluoroethylene grafts for hemodialysis access.

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.

Cardiac risk stratification using dipyridamole myocardial perfusion imaging and ambulatory ECG monitoring prior to vascular surgery.

Both dipyridamole myocardial perfusion imaging (cardiolite) and ambulatory ECG monitoring (Holter) for silent ischaemia have been found to be useful for stratification of cardiac risk in patients undergoing vascular surgery. The purpose of this study was to compare the diagnostic accuracy of these two non-invasive tests for prediction of perioperative cardiac events. One hundred patients (86 males, 14 females; mean age 67 +/- 8 years) underwent out-patient 48 h Holter monitoring and cardiolite imaging prior to vascular surgery (70 abdominal aortic aneurysm, 21 aortobifemoral, nine femoralpopliteal grafts). Ischaemia on Holter was defined as one or more episodes of ST segment depression 1 mm or greater, lasting 1 min or longer. Myocardial perfusion imaging was carried out with the high dose dipyridamole protocol (0.84 mg/kg), cardiolite and planar imaging. Ischaemia was defined as a segmental perfusion abnormality following dipyridamole with improved perfusion on rest imaging. Holter was positive for ischaemia in 34/100 patients (34%). Cardiolite scans were positive for ischaemia in 30/100 patients (30%). Perioperative myocardial infarction occurred in nine patients (two cardiac deaths). [table: see text] The diagnostic accuracy of the two tests was similar, with a low positive predictive value of 15-20%, and an extremely high negative predictive value of 94-96%. The event rate in patients with both tests negative was 2/48 (4.2%), with only one test positive 3/40 (7.5%) and with both tests positive 4/12 (33%). A reasonable approach to risk stratification would be to obtain either a Holter or cardiolite scan initially.(ABSTRACT TRUNCATED AT 250 WORDS)

Ancrod versus heparin for anticoagulation during vascular surgical procedures.

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.

Epidemiology of abdominal aortic aneurysm: the effect of differing definitions.

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).