Supraventricular arrhythmias in children and young adults with implantable cardioverter defibrillators.

INTRODUCTION: Rapidly conducted supraventricular tachycardias (SVTs) can lead to inappropriate device therapy in implantable cardioverter defibrillator (ICD) patients. We sought to determine the incidence of SVTs and the occurrence of inappropriate ICD therapy due to SVT in a pediatric and young adult population. METHODS AND RESULTS: We undertook a retrospective review of clinical course, Holter monitoring, and ICD interrogations of patients receiving ICD follow-up at our institution between March 1992 and December 1999. Of 81 new ICD implantations, 54 eligible patients (median age 16.5 years, range 1 to 48) were identified. Implantation indications included syncope and/or spontaneous/inducible ventricular arrhythmia with congenital heart disease (30), long QT syndrome (9), structurally normal heart (ventricular tachycardia/ventricular fibrillation [VT/VF]) (7), and cardiomyopathies (7). Sixteen patients (30%) received a dual-chamber ICD. SVT was recognized in 16 patients, with 12 of 16 having inducible or spontaneous atrial tachycardias. Eighteen patients (33%) received > or =1 appropriate shock(s) for VT/VF; 8 patients (15%) received inappropriate therapy for SVT. Therapies were altered after an inappropriate shock by increasing the detection time or rate and/or increasing beta-blocker dosage. No single-chamber ICD was initially programmed with detection enhancements, such as sudden onset, rate stability, or QRS discriminators. Only one dual-chamber defibrillator was programmed with an atrial discrimination algorithm. Appropriate ICD therapy was not withheld due to detection parameters or SVT discrimination programming. CONCLUSION: SVT in children and young adults with ICDs is common. Inappropriate shocks due to SVT can be curtailed even without dual-chamber devices or specific SVT discrimination algorithms.

Atrioventricular reciprocating tachycardia involving twin atrioventricular nodes in patients with complex congenital heart disease.

INTRODUCTION: Histologic studies of autopsy specimens described the coexistence of two distinct AV nodes (so-called "Minckeberg sling" or "twin AV nodes") in specific congenital heart defects; however, the clinical electrophysiologic (EP) characteristics of twin AV nodes have not been characterized in detail. METHODS AND RESULTS: Since April 1993, a total of seven patients with complex congenital heart disease presented with AV reciprocating tachycardia suspected to be mediated by twin AV nodes. A common anatomic finding was AV discordance ([S,L,L] or [I,D,D]) with a malaligned complete AV canal defect in 5 of 7 patients. Intracardiac EP study was performed in five cases, and ablation was attempted in three patients with successful elimination of tachycardia inducibility by interruption or modification of 1 of the 2 AV nodes. Important EP characteristics included (1) the existence of two discrete nonpreexcited QRS morphologies, each with an associated His-bundle electrogram; (2) decremental as well as adenosine-sensitive anterograde and retrograde conduction; and (3) inducible AV reciprocating tachycardia with anterograde conduction over one AV nodal pathway and retrograde conduction over the alternate AV nodal pathway. The existence of two AV nodes was further supported in the group treated with radiofrequency ablation by the development of transient accelerated junctional rhythm during energy delivery with an identical QRS morphology to that generated by anterograde conduction over the targeted AV node. CONCLUSION: Reciprocating tachycardia mediated by twin AV nodes can be a source of recurrent supraventricular tachycardia in patients with specific forms of complex congenital heart disease. Successful treatment with catheter ablation is possible.

Single-dose pharmacokinetics of sotalol in a pediatric population with supraventricular and/or ventricular tachyarrhythmia.

The pharmacokinetics (PK) of the antiarrhythmic sotalol, which elicits Class III and beta-blocking activity, has not been adequately defined in a pediatric population with tachyarrhythmias. The goal of this single-dose study with administration of sotalol HCl at a dose level of 30 mg/m2 body surface area (BSA) was to define the PK of the drug in the following four age groups: neonates (0-30 days), infants (1 month to 2 years), younger children (> 2 to < 7 years), and older children (7-12 years) with tachyarrhythmias of either supraventricular or ventricular origin. The drug was administered in an extemporaneously compounded syrup formulation prepared from the tablets containing sotalol HCl. For safety, vital signs and adverse events were recorded and the QTc interval and heart rate telemetrically monitored. Scheduled blood samples were taken over a 36-hour time interval following dose administration. The drug concentrations in plasma were measured by a sensitive and specific LC/MS/MS assay. Standard compartment model-independent methods were applied to compute the salient PK parameters of sotalol. Twenty-four clinical sites enrolled 34 patients. Thirty-three had analyzable data. Sotalol was rapidly absorbed, with mean peak concentrations occurring 2 to 3 hours after administration. The elimination of sotalol was characterized by an average half-life of between 7.4 and 9.2 hours in the four age groups. There existed statistically significant linear relationships between apparent total clearance (CL/f) or apparent volume of distribution (V lambda z/f) after oral administration and the covariates BSA, creatinine clearance (CLcr), body weight (BW), or age. The best predictors for CL/f were CLcr and BSA, whereas BW best predicted the V lambda z/f. The total area under the drug concentration-time curve in the smallest children with a BSA < 0.33 m2 was significantly greater than that in the larger children. This finding indicated that the BSA-based dose adjustment used in this study led to a larger exposure in the smallest children, whereas the exposure to the drug was similar in the larger children. The dose of 30 mg/m2 was tolerated well. No serious drug-related adverse events were reported. It can be concluded that the PK of sotalol in the pediatric patients depended only on body size, except for the neonates and smallest infants in whom the disposition of sotalol was determined by both body size and maturation of eliminatory processes.

Location of acutely successful radiofrequency catheter ablation of intraatrial reentrant tachycardia in patients with congenital heart disease.

Intraatrial reentrant tachycardia (IART) is common after surgery for congenital heart disease (CHD). Radiofrequency (RF) catheter ablation of IART targets anatomic areas critical to the maintenance of the arrhythmia circuit, areas that have not been well defined in this patient population. The purpose of this study was to determine the anatomic areas critical to IART circuits, defined by activation mapping and confirmed by an acutely successful RF ablation at the site. A total of 110 RF ablation procedures in 88 patients (median age 23.4 years, range 0.1 to 62.7) with CHD were reviewed. Patients were grouped according to surgical intervention: Mustard/Senning (n = 15), other biventricular repaired CHD (n = 24), Fontan (n = 43), and palliated CHD (n = 6). In first-time ablation procedures, > or = 1 IART circuits were acutely terminated in 80% of Mustard/Senning, 71% of repaired CHD, and 72% of Fontan (p = NS). The palliated CHD group underwent 1 of 6 successful procedures (17%), and this patient was excluded. The locations of acutely successful RF applications in Mustard/Senning patients (n = 14 sites) were at the tricuspid valve isthmus (57%) and at the lateral right atrial wall (43%). In patients with repaired CHD (n = 18 sites), successful RF sites were at the isthmus (67%) and the lateral (22%) and anterior (11%) right atria. In the Fontan group (n = 40 sites), successful RF sites included the lateral right atrial wall (53%), the anterior right atrium (25%), the isthmus area (15%), and the atrial septum (7%). Location of success was statistically different for the Fontan group (p = .002). In conclusion, the tricuspid valve isthmus is a critical area for ablation of IART during the Mustard/ Senning procedure and in patients with repaired CHD. IART circuits in Fontan patients are anatomically distinct, with the lateral right atrial wall being the more common area for successful RF applications. This information may guide RF and/or surgical ablation procedures in patients with CHD and IART.

Cardiac complications in pediatric patients on the ketogenic diet.

Cardiac complications of the ketogenic diet, in the absence of selenium deficiency, have not been reported. Twenty patients on the ketogenic diet at one institution were investigated. Prolonged QT interval (QTc) was found in 3 patients (15%). There was a significant correlation between prolonged QTc and both low serum bicarbonate and high beta-hydroxybutyrate. In addition, three patients had evidence of cardiac chamber enlargement. One patient with severe dilated cardiomyopathy and prolonged QTc normalized when the diet was discontinued.

Focal ablation of chaotic atrial rhythm in an infant with cardiomyopathy.

Chaotic atrial rhythm in infants has been defined similar to multifocal atrial tachycardia in adults, implying a multifocal etiology. However, its ECG appearance resembles atrial fibrillation, which sometimes has a unifocal ectopic mechanism amenable to catheter ablation. Curative focal radiofrequency ablation was performed in a 4-month-old infant with chaotic atrial rhythm and dilated cardiomyopathy. Left ventricular function subsequently returned to normal. Reversibility of associated cardiomyopathy supports aggressive rhythm management of chaotic atrial rhythm. In this patient, the unifocal origin allows insight into the pathophysiology of the rhythm and demonstrates the potential utility of catheter ablation for refractory cases.

Value of programmed ventricular stimulation in patients with congenital heart disease.

INTRODUCTION: The role of programmed ventricular stimulation (VSTIM) for risk stratification in congenital heart disease is unclear. We analyzed the results of VSTIM in selected congenital heart disease survivors at a single center to determine whether it improved the ability to predict a serious outcome. METHODS AND RESULTS: Between July 1985 and September 1996, 140 primary VSTIM studies were performed on 130 patients (median age 18.1 years, range 0 to 51). Tetralogy of Fallot (33 %), d-transposition of the great arteries (25 %), and left ventricular outflow tract obstruction (12%) accounted for the majority of patients. Indications included spontaneous ventricular tachycardia (VT) of > or = 3 beats (72%) and/or symptoms (68%). Sustained VT was induced in 25% of the studies, and nonsustained VT in 12%. Atrial flutter or other supraventricular tachycardia was documented in 32% and bradyarrhythmias in 26%. By univariate analysis, mortality was increased in patients with positive VSTIM versus negative VSTIM (18% vs 7%, P = 0.04). Using multivariate analysis, positive VSTIM was associated with a sixfold increased risk of decreased survival and a threefold increased risk of serious arrhythmic events, allowing up to 87% sensitivity in predicting mortality. However, 7 (33%) of 21 patients with documented clinical VT had false-negative studies. CONCLUSION: VSTIM in a large, selected group of congenital heart disease patients identified a subgroup with significantly increased mortality and sudden arrhythmic events. Failure to induce VT was a favorable prognostic sign, but the frequency of false-negative studies was high. Frequent supraventricular tachycardia further complicated risk stratification. Although VSTIM appears to be a reasonable tool for evaluation of this population, a larger, multicenter trial is recommended to clarify its utility.

Characteristics, management, and midterm outcome in infants with atrioventricular nodal reentry tachycardia.

Atrioventricular nodal reentry is a commonly recognized mechanism of supraventricular tachycardia (SVT) in adults, but is only rarely documented in the first year of life. The aim of this study was to elucidate characteristics, management, and outcome in infants with atrioventricular nodal reentrant tachycardia (AVNRT). Electrophysiologic studies performed between January 1988 and June 1996 were reviewed. Fifteen infants with AVNRT at 58 +/- 27 days (mean +/- SEM) were identified. Five had AVNRT detected following palliation of structural cardiac anomalies, including 4 with critical obstructions to left ventricular outflow. Typical AVNRT (ventriculoatrial interval 49 +/- 5 ms) was observed in 14 of 15 patients and atypical AVNRT (ventriculoatrial interval 191 +/- 22 ms) in 4 of 15. All patients received long-term therapy, beginning with digoxin in 13. Eight had symptomatic recurrences on digoxin and 6 of these were given beta blockers, with satisfactory control in 4. Three patients were controlled with class III agents, and 2 underwent slow pathway radiofrequency modification at ages 4.1 and 6.7 years, respectively. AVNRT was still inducible in 6 of 6 asymptomatic patients who underwent follow-up atrial stimulation studies after discontinuation of medical therapy. All 15 patients were alive with either absent or well-controlled AVNRT at age 45 +/- 7 months. We conclude that the course and outcome of AVNRT diagnosed in the first year of life are generally benign, but that a minority of patients have symptoms persisting beyond infancy. Digoxin is of questionable benefit in long-term control. AVNRT often remains inducible in asymptomatic patients, although the significance of this finding remains to be determined by long-term follow-up.

Use of an ultrasonic scalpel as an alternative to electrocautery in patients with pacemakers.

We report the safe and effective use of an ultrasonically activated scalpel as an alternative to unipolar electrocautery during surgical procedures in 4 patients with pacemakers. This scalpel provided adequate hemostasis without the adverse consequences of electromagnetic interference. As the scalpel was able to easily cut through the silicone connector sleeve of one generator, it is not recommended for routine generator replacement because it may damage existing pacing leads. However, its use during nonpacemaker operations in patients with pacemakers should be considered.

Long-term performance of bipolar epicardial atrial pacing using an active fixation bipolar endocardial lead.

Bipolar epicardial leads are not yet widely available for atrial use. Since September 1986, we have used a bipolar active fixation endocardial lead (Cardiac Pacemakers model number's 4266, 4268, and 4269) as a bipolar epicardial atrial lead by attaching the corkscrew tip to the atrial surface and imbricating atrial tissue around the more proximal electrode. A total of 77 bipolar epicardial atrial leads have been implanted using this approach in 72 patients with congenital heart disease (ages 3 months to 38.7 years; mean 8.9 +/- 8.8 years). Indications for atrial pacing included AV block (n = 46), sinus node dysfunction (n = 17), and antitachycardial pacing (n = 9). Indications for epicardial pacing included the presence of an intracardiac right to left shunt (n = 33), concomitant cardiac surgery (n = 26), surgeon preference (n = 7), and lack of transvenous access to the atrial endocardium (n = 6). Follow-up (median 23 months; mean 28.0 +/- 23.1 months; range 1-78 months) data beyond 1 month postimplantation were available for 44 leads. Atrial sensing was > or = 2.0 mV for 26 leads (59%) with sensing possible at > or = 0.75 mV for 42 leads (95%). Threshold data were available at 5 V for 37 leads and at 2.5 V for 36 leads with mean pulse width thresholds measuring 0.21 +/- 0.33 ms and 0.34 +/- 0.34 ms, respectively. Two leads failed (high capture thresholds at 5 days [n = 1], lead fracture at 42 months [n = 1]; one of which was replaced. Four additional leads were replaced electively (marginal thresholds [n = 1], intermittent phrenic nerve stimulation [n = 1], damaged during subsequent surgery [n = 1], clinically irrelevant insulation break [n = 1]) concomitant with additional cardiac surgery. Until a commercially available lead is developed and released, improvisation with a bipolar active fixation endocardial lead as a bipolar epicardial atrial lead is a reasonable approach to providing bipolar atrial sensing and pacing in patients for whom endocardial pacing is contraindicated.

Efficacy of radiofrequency ablation for control of intraatrial reentrant tachycardia in patients with congenital heart disease.

BACKGROUND: Intraatrial reentrant tachycardia (IART) is a common problem in patients with congenital heart disease (CHD). The progression of clinical symptoms of IART and their response to radiofrequency (RF) ablation are not yet well described. OBJECTIVES: The objective of the study was to determine the early and midterm success rates of RF ablation in effecting a reduction of clinical arrhythmic events in patients with IART and CHD. METHODS: Clinical records of patients undergoing early, successful RF ablation were analyzed retrospectively to document the occurrence and frequency of documented IART, cardioversion and arrhythmia-related hospital visits before and after ablation. RESULTS: Fifty-five catheterizations for intended RF ablation of IART were performed in 45 patients (mean [+/-SD] age 24.5 +/- 10.5 years, 40 after surgical palliation of CHD). Early success was achieved for one or more IART circuits in 33 patients (73%). Mean clinical follow-up of those patients with successful ablation is 17.4 +/- 11.3 months (total 574 patient-months). Documented IART recurrence was noted after 21 (53%) of 40 early, successful catheterizations in 17 (52%) of 33 patients, with a mean time to recurrence of 4.1 months, often with electrocardiographically novel configurations. A more prolonged and frequent history of IART was a univariate risk factor for recurrence. Seven patients underwent repeat RF ablations, and eight patients were restarted on antiarrhythmic medications after ablation. Two patients who had severe ventricular dysfunction before RF ablation died 1.5 and 11 months after RF ablation without known arrhythmia recurrence. Clinical events related to IART increased steadily in frequency for 24 months before RF ablation. Radiofrequency ablation resulted in a reduction of event frequency to levels significantly lower than those in the 12-month period before RF ablation and not significantly different from those levels observed at baseline 3 to 4 years before RF ablation. CONCLUSIONS: In patients with successful RF ablation, the frequency of subsequent events was reduced compared with the 2 preceding years. However, recurrence of IART in patients who showed clinical improvement was frequent, and often revealed the presence of new IART configurations.

High-rate atrial pacing as an innovative bridging therapy in a neonate with congenital long QT syndrome.

INTRODUCTION: The neonatal presentation of the long QT syndrome is rare, although it is frequently accompanied by life-threatening arrhythmias. Infants may not survive childhood despite traditional management with beta-adrenergic blockade and pacing. METHODS AND RESULTS: This case describes a newborn with a long QT interval, T wave alternans, intermittent 2:1 AV block, ventricular arrhythmias, and a family history of sudden death. After failing medical therapy, conventional VVI and DDD pacing were unsuccessful due to prolonged ventricular refractoriness and proarrhythmia. At 2 months of life, the child was treated with high-rate (180 ppm) atrial pacing to produce intentional 2:1 AV block. Following an episode of possible syncope at 16 months of age, an automatic implantable cardioverter defibrillator (ICD) was added. Finally, as recently reported, acutely induced hyperkalemia led to both a marked decrease in QTc and functional improvement in repolarization (consistent 1:1 AV conduction at rates to 180 beats/min). Spironolactone and dietary potassium were added and have produced the same effects chronically. CONCLUSIONS: High-rate atrial pacing with 2:1 AV block is presented as a novel and "bridging" therapy for neonatal long QT syndrome and 2:1 AV block with ventricular arrhythmias. Definitive therapy with ICD implantation was then possible when patient size was substantially increased. The electrophysiologic response to intentional elevation of the serum potassium suggests a genetic defect in an inward potassium channel and demonstrates a possible therapy of long QT syndrome in some future patients.

Spontaneous accelerated junctional rhythm: an unusual but useful observation prior to radiofrequency catheter ablation for atrioventricular node reentrant tachycardia in young patients.

Between May 1990 and March 1995, 5 of 29 young patients (ages 4.2-25 years; median 14.1 years) undergoing RF ablation for atrioventricular node reentrant tachycardia (AVNRT) presented with spontaneous accelerated junctional rhythm (AJR) (CL = 500-750 ms), compared to 0 of 58 age matched controls undergoing RF ablation for a concealed AV accessory pathway (P = 0.004). In 3 of the 5 patients with AVNRT and AJR, junctional beats served as a trigger for reentry. During attempted slow pathway modification in the five patients with AVNRT and AJR, AVNRT continued to be inducible until the AJR was entirely eliminated or dramatically slowed. These 5 patients are tachycardia-free in followup (median 15 months; range 6-31 months) with only 1 of the 5 patients continuing to experience episodic AJR at rates slower than observed preablation. Episodic spontaneous AJR is statistically associated with AVNRT in young patients and can serve as a trigger for reentry. Successful modification of slow pathway conduction may be predicted by the elimination of AJR or its modulation to slower rates, suggesting that the rhythm is secondary to enhanced automaticity arising near or within the slow pathway.

Five-year experience with radiofrequency catheter ablation: implications for management of arrhythmias in pediatric and young adult patients.

OBJECTIVE: A review of the results of the first 5 years of radiofrequency catheter ablation procedures performed at Children's Hospital, Boston, a large tertiary referral center for patients with congenital heart disease and arrhythmias common to the infant, child, and young adult. STUDY DESIGN: A retrospective review of 410 consecutive procedures in 346 patients who underwent at least one application of radiofrequency energy for the treatment of recurrent supraventricular or ventricular tachycardia. RESULTS: The overall final success rate for all diagnoses was 90%, with a higher success rate in patients with an accessory pathway (96%). During the 5-year study period, the success rate improved while the rates of failures and late recurrences declined. The incidence of serious complications was 1.2% (1 late death, 1 ventricular dysfunction, 1 complete heart block, 1 cardiac perforation, and 1 cerebrovascular accident). CONCLUSIONS: This report of a large series of radiofrequency catheter ablation procedures performed at an institution committed to treating congenital heart disease and pediatric arrhythmias confirms the safety and efficacy of this procedure. The pediatric cardiologist/electrophysiologist treating such patients must be aware of specific technical, anatomic, and electrophysiologic variations in the pediatric patient that are critical to the success of this therapy.

Low-temperature mapping predicts site of successful ablation while minimizing myocardial damage.

BACKGROUND: Temperatures near 50 degrees C can cause reversible loss of excitability in myocardial cells. METHODS AND RESULTS: Low-temperature, short-duration applications of radiofrequency energy were used to determine the adequacy of electrophysiological mapping of accessory pathway (AP) locations in 15 patients at 27 target sites using a closed-loop, temperature-controlled generator set to 50 degrees C. Energy was delivered until evidence of conduction block, or for a maximum of 10 seconds. If AP block occurred, a full 70 degrees C set point radiofrequency application was delivered to the same site. In the absence of AP block, tests with higher temperature settings (60 degrees C and 70 degrees C) were delivered to determine if inadequate temperature or catheter position led to failure of the initial 50 degrees C test. At 15 successful target sites where permanent AP block was achieved, the 50 degrees C test resulted in AP block in 14 (93%). Conduction returned in 13 of 14 APs after radiofrequency power was turned off. The time to block for the 70 degrees C applications was significantly shorter than for the 50 degrees C tests, and the peak temperature achieved was significantly higher. At unsuccessful sites where permanent AP block was not achieved, no block was induced with 11 of 12 tests at 50 degrees C, 6 of 6 tests at 60 degrees C, and 1 of 2 tests at 70 degrees C, suggesting that failure was due to incorrect catheter position. The sensitivity and positive predictive values of a 50 degrees C test identifying a successful site were > 90%. CONCLUSIONS: Low-temperature radiofrequency applications that cause transient AP block predict permanent success when a higher-temperature application is delivered at the same site. The time to achieve conduction block is a function of the temperature set point, and low-temperature tests produce reversible conduction block, suggesting minimal permanent injury.

Embolic complications associated with radiofrequency catheter ablation. Atakr Investigator Group.

Both early and late thromboembolic events are known complications of radiofrequency catheter ablation. This review of 758 patients undergoing 830 radiofrequency ablation procedures finds that embolic complications after radiofrequency ablation in patients without other risk factors for thromboembolism are rare (<0.2%).

Use of adenosine-sensitive nondecremental accessory pathways in assessing the results of radiofrequency catheter ablation.

Adenosine can cause conduction block in about 20% of nondecremental accessory pathways. Along with atrial activation mapping, adenosine may help differentiate retrograde AV node conduction versus residual accessory pathway conduction after radiofrequency catheter ablation; however, it is important to test the accessory pathway response to adenosine before ablation, particularly with a concealed accessory pathway.

Trends in HIV prevalence among disadvantaged youth. Survey results from a national job training program, 1988 through 1992.

OBJECTIVE: To describe trends in the prevalence of human immunodeficiency virus (HIV) among socially and educationally disadvantaged US youth. DESIGN: Analysis of demographic and geographic trends of HIV infection among Job Corps students from January 1988 through December 1992. SETTING: The Job Corps is a national training program for disadvantaged and out-of-school youth. POPULATION SCREENED: Youths aged 16 to 21 years who entered the Job Corps residential training centers during the survey period. MAIN OUTCOME MEASURE: Trends in prevalence of HIV infection among Job Corps students stratified by sex, age, race, and region of the country. RESULTS: Of the 269,956 Job Corps students screened, 812 (0.3%) tested positive for the antibody to HIV type 1. Seroprevalence of HIV for young men decreased from 3.6 per 1000 in 1988 to 2.2 per 1000 in 1992 (chi 2 test for trend, P < .001). Seroprevalence for young women increased from 2.1 per 1000 in 1988 to 4.2 per 1000 in 1990 (P = .001), with seroprevalence remaining stable from 1990 through 1992. The decreasing trends in HIV prevalence among men and increasing trends among women were primarily due to changes in seroprevalence in African-American students. CONCLUSIONS: The overall prevalence of HIV infection of three per 1000 is high, given the youth of Job Corps students. The significant rise in HIV rates among female Job Corps students provides evidence of the increasing risk of infection for socioeconomically disadvantaged young women. Reasons for the declining trend in HIV prevalence among male Job Corps students are not clear. Efforts to prevent the spread of HIV infection among adolescents must focus on the group that is hardest to reach--out-of-school and impoverished youth.

Expression of native and truncated forms of the human integrin alpha 1 subunit.

We report here the molecular cloning of cDNAs encoding for the human integrin alpha 1 subunit. The sequence is characteristic of an I domain containing integrin alpha subunit, with a high degree of homology to the rat integrin alpha 1 subunit, including complete identity of the transmembrane and cytoplasmic domains between the two species. The human cDNA directs the expression in mouse NIH 3T3 cells of authentic human alpha 1 protein as demonstrated by the reactivity of this subunit with two human-specific anti-alpha 1 monoclonal antibodies. This exogenous integrin specifically binds to type IV collagen in a Mg(2+)-dependent fashion. We have expressed in both transient systems and in stable cell lines truncated, soluble forms of the human alpha 1 subunit combined with truncated, soluble forms of beta 1 subunits. Although soluble beta 1 subunit was found in the media when the corresponding cDNA was used, the secretion of the soluble alpha 1 subunit was found to be dependent on dimerization with soluble beta 1. Co-transfection of truncated human alpha 1 cDNA with truncated forms of either the human or avian beta 1 cDNA led to efficient secretion of alpha 1.beta 1 heterodimers. These soluble heterodimers specifically bind to collagen IV in a manner similar to their full-length counterparts. Biosynthetic studies using stably expressing cell lines demonstrate that the soluble heterodimers and the native heterodimers are formed independently, strongly suggesting that the transmembrane or cytoplasmic domains of alpha and beta subunits are involved in the assembly of native heterodimers.

HIV infection in American Indians and Alaska Natives: surveys in the Indian Health Service.

A network of surveys of HIV seroprevalence in American Indians and Alaska Natives (AI/AN) was begun in 1989. From July 1, 1989 through June 30, 1991, 37,681 serologic specimens were collected from prenatal and sexually transmitted disease patients in 58 facilities operated or funded by the Indian Health Service. Specimens from AI/AN women receiving initial prenatal care showed an overall HIV prevalence of 0.3/1,000, while specimens obtained during the third trimester of pregnancy showed an overall prevalence of 1.0/1,000. The rate for rural third trimester prenatal patients (0.9/1,000) was similar to that for urban patients (1.1/1,000). HIV rates among third trimester AI/AN patients in three western states were 4 to 8 times higher than rates observed in childbearing women of all races in those states. The overall HIV seroprevalence in AI/AN seeking care for sexually transmitted diseases was 4.5/1,000 for males (urban 10.8/1,000; rural 2.0/1,000) and 0.7/1,000 for females (urban 0.9/1,000; rural 0.6/1,000). Approximately 1,210 to 4,250 (midpoint of range = 2,730) AI/AN in the U.S. are projected from survey findings to be currently infected with HIV. The presence of HIV in multiple specimens from rural areas and the similarity of HIV infection rates for female patients from rural and urban locations provides evidence of diffusion of the HIV epidemic to rural AI/AN, and emphasizes the need for effective HIV prevention for this population.