Clinical significance of low-positive troponin I by AxSYM and ACS:180.

We compared troponin I (TnI) assays (AxSYM [Abbott]; ACS:180 [Bayer]) in blood samples with concentrations less than 10 ng/mL (< 10 micrograms/L). Discordant results were evaluated by linearity studies and by testing for rheumatoid factor. Patients with discordant TnI results were compared with patients with concordant results and patients with negative TnI who had a new myocardial infarction or died within 2 months of initial testing. Positive TnI cutoffs by AxSYM and ACS:180 were 0.7 ng/mL (0.7 microgram/L) and 0.13 ng/mL (0.13 microgram/L), respectively. We identified 173 specimens that were repeatedly positive by at least 1 assay; 143 specimens were positive by both assays. Twenty samples positive for TnI by AxSYM were negative by ACS:180, while 10 samples positive by ACS:180 were negative by AxSYM. The discordant samples showed no evidence of interfering substances, including rheumatoid factor. Clinical follow-up showed that 26% of patients with elevated TnI by both assays, 33% with TnI positive only by AxSYM, 22% with TnI positive only by ACS:180, and 8% with negative TnI by AxSYM encountered at least 1 clinical end point. Variable detection rates by these assays for low-positive TnI represent a clinically significant problem.

Rabies and canine distemper in an arctic fox population in Alaska.

Two oil field workers were attacked by a rabid arctic fox (Alopex lagopus) in the Prudhoe Bay oil field (Alaska, USA) prompting officials to reduce the local fox population. Ninety-nine foxes were killed during winter 1994. We tested foxes for prevalence of rabies and canine distemper. Exposure to rabies was detected in five of 99 foxes. Of the five, only one fox had rabies virus in neural tissue as determined by the direct fluorescent antibody test. The other four foxes had been exposed to rabies, but had apparently produced antibodies and did not have an active infection. No evidence of canine distemper was detected as determined by the absence of distemper antibodies in serum and distemper virus in neural tissue.

Evaluation of the safety of two attenuated oral rabies vaccines, SAG1 and SAG2, in six Arctic mammals.

The safety of two attenuated oral rabies vaccines was evaluated in mink and in five species of rodents which occur in the Arctic. A 0.03 ml sample of liquid vaccine was installed directly into the mouth of voles and lemmings and 0.1 ml into the mouth of Arctic ground squirrels and mink. Animals were euthanized at 36 and 46 days postexposure; brain tissue was analyzed by FAT and serum by RFFIT. No rabies deaths occurred in 47 animals tested. Four animals representing three rodent species seroconverted, the highest titer being 0.5 IU ml-1. The absence of rabies virus in brain tissue indicates the safety of these vaccines in these species. The replacement of arginine with glutamic acid at position 333 reduces the pathogenicity of these vaccines, thereby presumably preventing the deleterious effect of viral entry into CNS neurons.

Occurrence of rabies in a wolf population in northeastern Alaska.

Nine Alaskan wolves (Canis lupus) were found dead during spring and summer 1985; five of seven animals tested for rabies virus were positive. The 1985 epizootic altered annual den use patterns by wolves in northeastern Alaska, but did not appear to affect population size. We propose that rabies in arctic wolves may be more common than previously thought.

Survey of fox trappers in northern Alaska for rabies antibody.

The purpose of this research was to determine whether trappers in northern Alaska acquired immunity to rabies virus from non-bite exposures while trapping and skinning arctic foxes (Alopex lagopus). In coastal Alaska recurring epizootics presumably provide trappers ample opportunity for contact with rabid animals. Serum neutralization analyses of blood samples collected from 26 individuals were conducted. All but three had negative rabies neutralizing antibody levels (< 0.05 I.U./ml). Two of these had previously received rabies vaccine but one individual who had trapped for about 47 years with an estimated harvest of over 3000 foxes and who had never received pre- or post-exposure rabies vaccination had a rabies serum neutralizing antibody concentration of 2.30 I.U./ml. This represents the first report of an unvaccinated person acquiring rabies virus antibody with a titre above the 0.5 I.U./ml level considered acceptable by the World Health Organization.

Oral rabies vaccination of arctic foxes (Alopex lagopus) with an attenuated vaccine.

Arctic foxes were immunized with the SAG1 oral rabies vaccine. The effectiveness was determined by the serological response and by the survival to a challenge dose of rabies virus from an Alaskan fox. Vaccine virus was isolated from saliva 1 h after the liquid vaccine was placed directly into the mouth but not subsequently (tested up to 1 week postvaccination). Two weeks after vaccination, protective antibody levels were present in all foxes and all vaccinated foxes survived challenge at 9 weeks postvaccination. At 26 weeks postvaccination (17 weeks postchallenge) all but one fox had detectable antibody levels. Neural tissue harvested from surviving foxes was negative for rabies virus by direct immunofluorescent testing. One of the foxes vaccinated with SAG1 seroconverted and survived challenge even though the titre of the vaccine used was almost 4 logs less than that used to vaccinate the other foxes. These results suggest that the avirulent SAG1 oral rabies vaccine is very effective in protecting arctic foxes.

Expression of largest RNA segment and synthesis of VP1 protein of bluetongue virus in insect cells by recombinant baculovirus: association of VP1 protein with RNA polymerase activity.

The bluetongue virus core particles have been shown to contain an RNA-directed RNA polymerase (1). To identify the protein responsible for the virion RNA polymerase activity, the complete 3.9 Kb DNA clone representing the largest RNA segment 1 (L1) of bluetongue virus (BTV-10) was placed under control of the polyhedrin promoter of Autographa californica nuclear polyhedrosis virus (AcNPV). The derived recombinant virus was used to infect Spodoptera frugiperda cells. As demonstrated by stained polyacrylamide gel electrophoresis and by the use of bluetongue virus antibody, infected insect cells synthesized the largest protein of BTV-10 (VP1, 150 k Da). Antibody raised in rabbit to recombinant VP1 protein recognized bluetongue virus VP1 protein. The recombinant virus infected cell lysate had significantly inducible levels of RNA polymerase enzymatic activity as determined by a poly (U)-oligo (A) polymerase assay. The availability of enzymatically active bluetongue virus RNA polymerase provides a system in which we can precisely delineate the role this protein plays in the regulation of bluetongue replication.

Genetic relationships of bluetongue virus serotypes isolated from different parts of the world.

Full-length DNA clones representing the 10 double-stranded RNA segments of US bluetongue virus serotype 10 (BTV-10) have been used in a study to determine the genetic relationships among 20 different BTV serotypes. The study was undertaken using Northern blot hybridization techniques involving 32P-labelled DNA probes and total RNA species extracted from BHK-21 cells infected with 20 different BTV serotypes. The results obtained indicate that all the genes representing the nonstructural proteins of BTV (NS1, NS2 and NS3) as well as most of the inner capsid polypeptides are highly conserved (e.g., VP1, VP3, VP4), while VP6 and VP7, the remaining two inner capsid components, are less conserved. The genes representing the two outer capsid polypeptides, VP2 and VP5, vary significantly. When complete DNA clones of RNA segment 2 (representing the VP2 neutralization gene) of 4 other US serotypes (BTV-2, -11, -13 and -17) and one Australian serotype (BTV-1) were used in similar hybridization studies, the data obtained showed that despite geographical distances, a certain BTV serotype exhibits similarities. Some hybridization signals were detected with several of the inner capsid genes and the corresponding RNA segments of epizootic hemorrhagic disease virus (EHDV), a distantly related orbivirus, although none of the BTV outer capsid genes, nor any of the nonstructural genes hybridized with either EHDV-1 or EHDV-2 RNA species.

Immunization of arctic foxes (Alopex lagopus) with oral rabies vaccine.

Arctic foxes (Alopex lagopus) were successfully immunized against rabies using an orally-administered, liquid SAD-BHK21 live virus vaccine in a sausage bait. Immunization was determined by serologic response and by resistance to challenge with an arctic rabies virus strain. Virus was not shed in saliva following oral vaccination, indicating that arctic foxes would not infect other foxes after ingesting this vaccine. High antibody levels were present in all experimental foxes 2 wk following initial vaccination. A booster vaccination at 56 wk induced a significant serologic response within 1 wk, suggesting an anamnestic response but titers began to decline within 8 wk in most foxes. Foxes were observed for 16 mo following the challenge and exhibited no symptoms of rabies. The SAD-BHK21 rabies vaccine in a sausage bait system has a strong potential for vaccinating wild populations of arctic fox.

Isolated atrial septal defect with pulmonary vascular obstructive disease--long-term follow-up and prediction of outcome after surgical correction.

UNLABELLED: We examined the cases of 702 patients found to have isolated atrial septal defect of the secundum or sinus venosus type at catheterization from 1953 to 1978. Forty patients (6%), 34 women and six men, had pulmonary vascular obstructive disease, with a total pulmonary resistance greater than 7 U/m2; of these patients 26 (mean age 47 years) underwent surgical closure and 14 (mean age 44 years) received medical treatment. All patients were followed for at least 4 years, with a median follow-up of 12 years. At the most recent follow-up, 17 of the 40 patients were dead. Of the 22 surgically treated patients with total pulmonary resistance less than 15 U/m2, 19 were alive with significant regression of symptoms. All four surgically treated patients with total pulmonary resistance greater than or equal to 15 U/m2 were dead. Of the five medically treated patients with total pulmonary resistance less than 15 U/m2, four had died, and one was alive with significant progression of symptoms. Of the nine medically treated patients with total pulmonary resistance greater than or equal to 15 U/m2, six had died and the three survivors had progression of symptoms. In the surgically treated group, the following variables correlated with survival: total pulmonary resistance (p less than .00001), pulmonary arteriolar resistance (p less than .00001), pulmonary-to-systemic resistance ratio (p = .004), systemic arterial oxygen saturation (p = .005), and pulmonary arterial oxygen saturation (p = .007). IN CONCLUSION: (1) Atrial septal defect with high total pulmonary resistance is uncommon and predominates in adult female patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma marking of arctic foxes with iophenoxic acid.

Six arctic foxes (Alopex lagopus) were marked with iophenoxic acid (IA), a substance which elevates concentrations of protein-bound iodine in blood plasma. Buccal absorption of IA was determined by placing 20 mg IA dissolved in 100% ethyl alcohol on the tongue. Blood samples collected from 1 to 36 wk following exposure showed that all foxes were marked already at 1 wk and continued until 13 wk; two foxes were still marked at 36 wk. Clearance rates for iodine varied with initial dose response, and those foxes with high 1-wk iodine concentrations excreted iodine more rapidly than those with lower initial concentrations; by 13-wk excretion rates were similar.

Replacement of obstructed extracardiac conduits with autogenous tissue reconstructions.

Tissue-valved prosthetic extracardiac conduits fail in 6% to 30% of patients within 5 years of implantation. Failure is caused both by valve degeneration and by conduit peel formation. This report describes a technique, performed in 16 children, in which an obstructed right ventricle-to-pulmonary artery valved conduit was removed and a new conduit constructed using the conduit bed as the posterior wall and a patch of xenograft pericardium (n = 10), homograft dura mater (n = 5), or Dacron (n = 1) as the roof of the conduit. One child with pulmonary hypertension required a Björk-Shiley pulmonary valve; in the others no valve was inserted. This technique simplifies conduit replacement, allows for a generous-sized outflow tract that may grow with patient growth, and uses material unlikely to become obstructed.

Progressive atrioventricular block during exercise in univentricular heart.

Two patients who had univentricular heart presented with complaints of recurrent nausea and vomiting during exertion. Exercise study revealed 1:1 atrioventricular conduction and no symptoms at rest; at peak exercise, both patients experienced progressive, high grade, second degree atrioventricular block and nausea. Both patients underwent permanent pacemaker implantation, with relief of symptoms. Exercise testing is important in evaluating patients who are at increased risk of spontaneous atrioventricular block, and exertion-induced nausea may be a clue to its presence.

Pulmonary artery thrombosis associated with anomalous pulmonary venous connection: an unusual complication following the modified Fontan procedure.

The presence of unrecognized partial anomalous pulmonary venous connection may cause complications of pulmonary infarction and right-to-left shunting in patients undergoing the modified Fontan procedure. These complications can be prevented by identification of any anomalous pulmonary venous connection at preoperative cardiac catheterization.

Fifteen-year experience with surgical repair of truncus arteriosus.

From 1965 until March, 1982, 167 patients underwent surgical repair of truncus arteriosus. The age at operation ranged from 18 days to 33 years (mean 6 years). There were 48 hospital deaths (28.7%). The following factors had a positive correlation with the possibility of a surgical death: age at operation less than 2 years (p less than 0.001), a postrepair pulmonary arterial/left ventricular pressure ratio greater than 0.5 for patients with two pulmonary arteries (p less than 0.001) and greater than 0.6 for patients with unilateral absence of a pulmonary artery (p less than 0.02), and a postrepair right ventricular/left ventricular pressure ratio greater than 0.8 (p less than 0.008). The 119 hospital survivors were followed up for a total of 829 person-years. Late survival rate at 5 years was 84.4% and at 10 years, 68.8%. Preoperative factors that correlated with a reduced long-term survival rate were as follows: increasing age at operation (p = 0.004), the presence of moderate or severe truncal valve insufficiency (p = 0.008), lower pulmonary/systemic flow ratio (p = 0.04), and unilateral absence of a pulmonary artery (p less than 0.001). Thirty-six patients required reoperation during the follow-up period (30%) primarily for replacement of the right ventricular-pulmonary arterial conduit and/or for truncal valve replacement. The long-term results obtained in these patients support the need for early repair of the anomaly, improvement in the methods for control or repair of the truncal valve insufficiency, and the continued search for better extracardiac valved conduits.

Survival in atrioventricular discordance.

Limited information is available concerning the long-term survival of patients with atrioventricular discordance, ventriculoarterial discordance, and two ventricles (corrected transposition). The long-term follow-up of 107 patients examined at the Mayo Clinic over a 30-year period between 1951 and 1981 was reviewed. Overall survival from the date of Mayo Clinic diagnosis was 70% at five years and 64% at ten years. Associated variables were analyzed for their effect on survival including sex, age at diagnosis, presence of ventricular septal defect, pulmonary stenosis, dextrocardia, left atrioventricular valve insufficiency, and complete heart block. There was no significant difference between those with and without a ventricular septal defect (VSD). Pulmonary stenosis was protective when a VSD was present but was not a significant predictor of long-term survival. The only variable that consistently correlated with decreased survival was left atrioventricular valve insufficiency (p less than 0.04 for univariate and stepwise Cox, and p = 0.08 for multivariate analysis). A logistic model for survival after open-heart surgery failed to identify any significant variable. We conclude that the presence of left atrioventricular valve insufficiency in association with atrioventricular discordance significantly alters the long-term outcome. Atrioventricular valve replacement should be considered in such patients when insufficiency becomes hemodynamically significant.

Results of the Damus-Stansel-Kaye procedure for transposition of the great arteries and for double-outlet right ventricle with subpulmonary ventricular septal defect.

From 1975 through 1982, the Damus-Stansel-Kaye procedure was performed on 20 patients with complete transposition of the great arteries (TGA) and on 4 with double-outlet right ventricle (DORV) and subpulmonary ventricular septal defect (VSD). The patients ranged from 6 days to 20 years old (median age, 13 months). Associated anomalies included atrial septal defect (24 patients), VSD (14), and others (25). Thirteen patients had had palliative operations previously. Of the 14 hospital deaths (58%), 13 occurred among the 17 patients with one or more risk factors: age less than 18 months, weight less than 10 kg, and left ventricular peak systolic pressure less than 75% of systemic pressure. Follow-up ranged from 12 to 87 months (mean, 51 months). One patient died of cardiac failure two years postoperatively, and 2 required conduit replacement at 40 and 50 months because of stenosis. All 9 survivors are free from major symptoms. The Damus-Stansel-Kaye repair is most suitable for patients with TGA or DORV with subpulmonary VSD who are older than 18 months, weight more than 10 kg, and have a "prepared left ventricle," and whose coronary artery anatomy precludes transplantation.

Functional assessment of the Fontan operation: combined M-mode, two-dimensional and Doppler echocardiographic studies.

Combined M-mode, two-dimensional and Doppler echocardiographic studies were used to assess the postoperative status of 33 patients who had undergone the modified Fontan procedure. Twenty-four patients had surgical repair with use of a simple direct right atrium to pulmonary artery anastomosis. The remaining patients had repair with use of a prosthesis or associated Glenn shunt. Twenty-seven patients were studied early in the postoperative period (2 months or less) and the remaining patients were studied up to 6 years postoperatively. A total of 36 examinations were performed. Of the 33 patients, 13 had tricuspid atresia, 12 had double inlet left ventricle with hypoplastic right ventricular outlet chamber and 8 had complex lesions with atrioventricular canal, double outlet right ventricle or a hypoplastic ventricle. Postoperative assessment by M-mode and two-dimensional echocardiography demonstrated normal or mildly reduced ventricular function (ejection fraction greater than 40%) in 22 patients. In 24 patients, a "normal" flow pattern was observed in the pulmonary artery by pulsed Doppler echocardiography, with predominant diastolic flow and accentuation by atrial systole somewhat similar to the venous flow pattern observed in the superior vena cava. "Abnormal" flow patterns (disorganized systolic flow, absence of atrial waves and little or no increase with inspiration) were observed in nine patients with reduced ventricular function or residual shunt. Continuous wave Doppler study also demonstrated mild dynamic subaortic obstruction in two patients. Combined pulsed and continuous wave studies showed atrioventricular valve insufficiency in 10 patients. Follow-up studies revealed a satisfactory clinical course in most patients. Three patients died approximately 4 to 8 months after their Fontan operation.