JS Gammie, M Zenati, RL Kormos, BG Hattler, LM Wei, RV Pellegrini, BP Griffith, and CM Dyke. 1998. “Abciximab and excessive bleeding in patients undergoing emergency cardiac operations.” Ann Thorac Surg, 65, 2, Pp. 465-9.Abstract
BACKGROUND: Abciximab (ReoPro; Eli Lilly and Co, Indianapolis, IN) is a monoclonal antibody that binds to the platelet glycoprotein IIb/IIIa receptor and produces powerful inhibition of platelet function. Clinical trials of abciximab in patients undergoing coronary angioplasty have demonstrated a reduction in thrombotic complications and have encouraged the widespread use of this agent. We have observed a substantial incidence of excessive bleeding among patients who receive abciximab and subsequently require emergency cardiac operations. METHODS: The records of 11 consecutive patients who required emergency cardiac operations after administration of abciximab and failed angioplasty or stent placement were reviewed. RESULTS: The interval from the cessation of abciximab administration to operation was critical in determining the degree of coagulopathy after cardiopulmonary bypass. The median values for postoperative chest drainage (1,300 versus 400 mL; p < 0.01), packed red blood cells transfused (6 versus 0 U; p = 0.02), platelets transfused (20 versus 0 packs; p = 0.02), and maximum activated clotting time (800 versus 528 seconds; p = 0.01) all were significantly greater in the early group (cardiac operation < 12 hours after abciximab administration; n = 6) compared with the late (cardiac operation >12 hours after abciximab administration; n = 5) group. CONCLUSIONS: This report suggests that the antiplatelet agent abciximab is associated with substantial bleeding when it is administered within 12 hours of operation.
HA Cohen, M Zenati, AJ Smith, JS Lee, S Chough, Z Jafar, P Counihan, M Izzo, JE Burchenal, AM Feldman, and B Griffith. 1998. “Feasibility of combined percutaneous transluminal angioplasty and minimally invasive direct coronary artery bypass in patients with multivessel coronary artery disease.” Circulation, 98, 11, Pp. 1048-50.Abstract
BACKGROUND: Angioplasty has become an accepted treatment of patients with coronary artery disease and is now commonly used to treat patients with multivessel disease. The major disadvantage of angioplasty has been restenosis requiring repeat interventions with resultant loss of initial cost savings. Compared with the right and the circumflex coronary arteries, the left anterior descending artery (LAD) has been more adversely affected by restenosis. Recently, minimally invasive direct coronary artery bypass (MIDCAB) to the LAD through a small left anterior thoracotomy using the left internal mammary artery has been performed in some centers with excellent early results and with reduced costs compared with standard bypass surgery. METHODS AND RESULTS: We retrospectively reviewed the first 31 consecutive patients treated in our institution with integrated coronary revascularization (ICR): MIDCAB to the LAD combined with PTCA of the other diseased vessels in patients with multivessel disease. Postoperative angiography in 84% of patients revealed a patent anastomosis and normal flow in the graft and bypassed vessel. Thirty-eight (97%) of 39 vessels were successfully treated percutaneously. At a mean follow-up of 7 months, all patients are currently asymptomatic. There have been 2 adverse clinical events, both related to angioplasty and not to MIDCAB. The average length of stay at the hospital after MIDCAB was 2.79+/-1.05 days. CONCLUSIONS: These preliminary results with ICR are encouraging and suggest that a randomized, prospective clinical trial comparing ICR with standard coronary artery bypass surgery for the revascularization of symptomatic patients with multivessel disease involving the LAD is warranted.
M Zenati, RJ Keenan, AP Courcoulas, and BP Griffith. 1998. “Lung volume reduction or lung transplantation for end-stage pulmonary emphysema?” Eur J Cardiothorac Surg, 14, 1, Pp. 27-31; discussion 31-2.Abstract
OBJECTIVE: As the waiting period for lung transplant (LT) candidates with end-stage pulmonary emphysema (COPD) continues to increase, there is a need for alternative treatments to reduce the morbidity and mortality associated with COPD. We hypothesized that lung reduction (LR) may avoid the need for subsequent LT in patients on the waiting list that are also candidates for LR. METHODS: From July 1994 to December 1995, 20 patients received LR as alternative to LT. The average age was 58 +/- 7 years; 11 were males. Eighteen patients had primary COPD and two had alpha-1 antitrypsin deficiency. Eighteen LRs were thoracoscopic (two bilateral and 16 unilateral) and two were done through a median sternotomy. RESULTS: At a follow-up of 32 +/- 4 months, 19 patients are alive (19/20 = 95%). Fifteen patients (15/20 = 75%) are currently off the LT list and doing well: FEV1 is 40 +/- 18% predicted at 2 years compared with 22.7 +/- 6% before LR (P < 0.001); FVC is 84 +/- 13% at 2 years compared with 55 +/- 7% (P < 0.001) and the RV is 145 +/- 59% compared with 270 +/- 58% (P < 0.001). One patient (5%) required extra-corporeal membrane oxygenation (ECMO) after LR to the contralateral side of the first procedure and subsequently died. Two patients (10%) are currently listed for LT because of persistent symptoms. One patient (5%) in whom deterioration was secondary to exposure to toxic fumes, underwent successful LT. One patient (5%) is doing well from the pulmonary standpoint but is being worked up for new severe coronary artery disease (CAD). The freedom from LT is 95% (19/20) and the freedom from repeat LR is 85% (17/20). CONCLUSIONS: LR has the potential to offer an effective palliative alternative to LT in 75% of selected patients up to 32 months of follow-up. Widespread use of bilateral LR is anticipated to further improve the results.
R Holubkov, M Zenati, JJ Akin, L Erb, and A Courcoulas. 1998. “MIDCAB characteristics and results: the CardioThoracic Systems (CTS) registry.” Eur J Cardiothorac Surg, 14 Suppl 1, Pp. S25-30.Abstract
OBJECTIVE: The CardioThoracic Systems (CTS) registry of minimally invasive direct coronary artery bypass (MIDCAB) was established to examine baseline characteristics of patients undergoing this surgical procedure, document details of the procedures including grafting techniques and post-operative complication rates, and assess post-operative graft patency. METHODS: A total of 508 consecutive patients who had MIDCAB using CTS instrumentation between April 1996 and March 1997 at 35 international centers were analyzed. RESULTS: The mean age of patients, 27% of whom were women, was 63 years. Eight percent had previous coronary artery bypass surgery. While nearly all patients had significant stenoses in the left anterior descending artery, 23% had disease in two vessels and 9% in three vessels. Almost all procedures used the left internal mammary artery, with 7% employing multiple or sequential grafts. The entire surgical procedure lasted on average 135 min (median 2 h), with a mean time of 14 min to perform anastomosis. Surgical approaches, including anastomosis technique and method used to maintain bloodless field, varied widely across clinical centers. In-hospital complication rates were relatively low, with 0.6% mortality (0% perioperative), 1.2% conversion to sternotomy with cardiopulmonary bypass, 1.4% conversion to sternotomy without bypass, and 5.5% redo or reintervention. In total, 92% of patients were free from all of these events at hospital discharge; women showed a strong trend toward increased risk for major in-hospital events compared with men. Rib fracture was the most common complication, reported in 12% of patients. Post-operative angiography, performed in 83 patients at an average 2.2 days post-procedure, found full patency in 78 (94%). CONCLUSIONS: The CTS registry data indicates that in the great majority of patients, MIDCAB using CTS instrumentation was performed safely and with acute success. Comparative studies, most importantly clinical trials, are needed to determine the types of patients who benefit most from this procedure, as well as its longer-term outcome.
M Zenati, HA Cohen, R Holubkov, AJ Smith, AJ Boujoukos, J Caldwell, L Firestone, and BP Griffith. 1998. “Preoperative risk models for minimally invasive coronary bypass: a preliminary study.” J Thorac Cardiovasc Surg, 116, 4, Pp. 584-9.Abstract
OBJECTIVE: Available risk assessment models are designed for standard coronary artery bypass grafting. We hypothesized that minimally invasive coronary bypass could improve on predicted outcome in extremely high-risk patients (Parsonnet score > 20%) by the current risk models. METHODS: From September 1996 to September 1997, 27 consecutive extremely high-risk patients underwent minimally invasive coronary bypass. Seventeen patients were male; age was 73 +/- 12 years, and 63% of patients were older than 75 years. Left ventricular ejection fraction was 33.7% +/- 15% and 63% had an ejection fraction of less than 35%. The predicted 30-day mortality according to the System 97 model was 25.6% +/- 11.3%. The Parsonnet risk score was 36.2% +/- 11%; the predicted length of stay in the hospital was 15.3 +/- 3 days. The predicted risk of stroke according to the Multicenter Perioperative Stroke Risk Index was 22.3% +/- 11.7%. RESULTS: Minimally invasive coronary bypass was isolated in 20 patients and integrated with angioplasty and stenting in 7 patients. The observed 30-day mortality was 0% (P < .01 vs predicted): at an average follow-up of 10.8 +/- 4.1 months, 26 patients (96.3%) are alive without angina; one patient with acquired immunodeficiency syndrome died on postoperative day 40 of acute pancreatitis. No patient had a stroke or neurologic deficit (P < .01 vs predicted). Patency of internal thoracic artery anastomosis was confirmed by angiography in all 27 patients. No patient required reoperation. Eighteen patients (67%) were extubated in the operating room. The observed length of hospital stay after minimally invasive coronary bypass was 3.8 +/- 2.6 days (P < .01 vs predicted). CONCLUSION: On the basis of our results on a relatively small series of patients, we suggest that risk models geared for standard coronary bypass grafting may not be appropriate for minimally invasive coronary bypass.
M Zenati, L Spier, JS Gammie, and BP Griffith. 1998. “Resident training and minimally invasive cardiac surgery.” J Thorac Cardiovasc Surg, 115, 6, Pp. 1390.
FA Pigula, BP Griffith, MA Zenati, JH Dauber, SA Yousem, and RJ Keenan. 1997. “Lung transplantation for respiratory failure resulting from systemic disease.” Ann Thorac Surg, 64, 6, Pp. 1630-4.Abstract
BACKGROUND: Lung transplantation for pulmonary failure resulting from systemic disease is controversial. We reviewed our transplant experience in patients with sarcoidosis, scleroderma, lymphangioleiomyomatosis, and graft-versus-host disease. METHODS: This retrospective review examined the outcome of 23 patients who underwent pulmonary transplantation for these systemic diseases. Group 1 included 15 patients with pulmonary hypertension who underwent transplantation (9 for sarcoidosis, 6 for scleroderma), and group 2 included 8 patients with normal pulmonary artery pressures who underwent transplantation (5 for lymphangioleiomyomatosis, 3 for graft-versus-host disease). The incidences of infection and rejection, pulmonary function, and survival were measured and compared with those of patients who underwent transplantation for isolated pulmonary disease. RESULTS: Although there were no differences in the rate of infection between patients who underwent transplantation for systemic versus isolated disease, patients with pulmonary hypertension who underwent transplantation for systemic disease had significantly lower rates of rejection. Four patients with sarcoidosis and 2 with lymphangioleiomyomatosis demonstrated recurrence in the allograft. Survival was similar between patients who underwent transplantation for systemic versus isolated disease. CONCLUSIONS: Patients with respiratory failure resulting from these systemic diseases can undergo transplantation with outcomes comparable to those obtained in patients who undergo transplantation for isolated pulmonary disease.
M Zenati, TM Domit, M Saul, J Gorcsan, WE Katz, M Hudson, AP Courcoulas, and BP Griffith. 1997. “Resource utilization for minimally invasive direct and standard coronary artery bypass grafting.” Ann Thorac Surg, 63, 6 Suppl, Pp. S84-7.Abstract
BACKGROUND: Minimally invasive direct coronary artery bypass grafting (MIDCABG) has been recently reintroduced into the cardiac surgical armamentarium for selected patients with suitable coronary anatomy. We hypothesized that MIDCABG had the potential for similar immediate results with decreased perioperative morbidity and decreased resource utilization compared with standard coronary artery bypass grafting (CABG). METHODS: From January 1996 to August 1996, 17 MIDCABG patients were compared with 33 patients with left ventricular ejection fraction greater than 0.50 who underwent CABG with standard technique. No significant differences were observed between the two groups for preoperative variables that are known to affect cost and resource utilization. Length of stay in the hospital was 2.5 +/- 0.8 days for MIDCABG and 5.9 +/- 2 days for CABG (p < 0.0001); length of stay in the intensive care unit was 12.3 +/- 3.3 hours for MIDCABG compared to 32.3 +/- 12.6 hours for the CABG group (p < 0.0001). RESULTS: Forty-one percent of MIDCABG patients were extubated in the operating room and 59% were discharged home on the first or second postoperative day versus none in the CABG group (p < 0.0001). Significantly less morbidity was observed in the MIDCABG group compared with CABG. Total ratio of cost-to-charge was $12,885 +/- $1,511 for MIDCABG and $21,260 +/- $5,497 for CABG (p < 0.0001), with an average savings of $8,375. CONCLUSIONS: Minimally invasive CABG is associated with significant reduction of resource utilization and morbidity related to inital hospitalization compared with CABG.
M Zenati, SM Pham, RJ Keenan, and BP Griffith. 1996. “Extracorporeal membrane oxygenation for lung transplant recipients with primary severe donor lung dysfunction.” Transpl Int, 9, 3, Pp. 227-30.Abstract
Primary severe donor lung dysfunction (DLD) is a significant complication after lung transplantation (LTx), and a high mortality is reported with conventional therapy. The purpose of this report is to review the experience of the University of Pittsburgh with extracorporeal membrane oxygenation (ECMO) for primary severe DLD after LTx. From September 1991 to May 1995, 220 LTx were performed at our center. Eight patients (8/220 = 3.6%) with severe DLD after LTx required ECMO support. The age of LTx recipients was 44 +/- 5 years (mean +/- SD); seven patients were female and one was male. Indications for LTx were: chronic obstructive pulmonary disease in four patients, bronchiectasis in two, and pulmonary hypertension in two. There were three single LTx and five bilateral LTx. The interval from LTx to institution of ECMO was 5.6 +/- 3.2 h (range 0-10 h). Three patients were supported with veno-venous (v-v) ECMO and five had veno-arterial (v-a) ECMO. The duration of ECMO support was 7.3 +/- 4.8 days (range 3-15 days). activated glotting time (ACT) was maintained between 110 and 180 s with intermittent use of heparin. Seven patients (7/8 = 87%) were successfully weaned from ECMO and six patients (6/8 = 75%) were discharged home; they are currently alive after a follow-up of 17 +/- 10.1 months. One patient died on ECMO support for refractory DLD and another died 2 months after ECMO wean from multisystem organ failure. At 6 months follow-up, forced expiratory volume in 1 s (FEV1) is 2.35 +/- 0.91 (75% +/- 17.4% predicted) and mean forced vital capacity (FVC) is 2.53 +/- 0.81 (64% +/- 14% predicted). We conclude that ECMO can be lifesaving when instituted early after primary severe DLD. The v-v ECMO support is preferred when the patient is hemodynamically stable and adequate long-term function of the allograft is anticipated.
M Zenati, RJ Keenan, FC Sciurba, JD Manzetti, RJ Landreneau, and BP Griffith. 1996. “Role of lung reduction in lung transplant candidates with pulmonary emphysema.” Ann Thorac Surg, 62, 4, Pp. 994-9.Abstract
BACKGROUND: The average waiting time for candidates for lung transplantation (LTx) with end-stage emphysema is 21 months with a 15% mortality. We hypothesized that lung reduction might offer an alternative to LTx. METHODS: Of 95 patients with end-stage emphysema evaluated by our LTx program, 45 were accepted for both lung reduction and LTx and 35 underwent lung reduction. RESULTS: All 35 patients survived lung reduction. Thirty patients had a follow-up of 3 months. There was a significant improvement (p < 0.05) of forced expiratory volume in 1 second (0.64 to 0.97 L), forced vital capacity (2.12 to 2.76 L), residual volume (5.62 to 4.26 L), maximum voluntary ventilation (28.1 to 38.5 L/min), 6-minute walk (904 to 1,012 feet), Borg dyspnea index (3.7 to 2.4), and arterial carbon dioxide tension (44.9 to 41.6 mm Hg). Twenty patients (66%) were removed from the LTx list due to their significant improvement (group A). Compared with the remaining 10 patients with 3 months of follow-up (group B), percent increase in forced expiratory volume in 1 second (70% in group A versus 27% in group B) and in forced vital capacity (41% group A versus 18% group B) and percent decrease in residual volume (26% group A versus 1.5% group B) were significantly better in group A (p < 0.01). Seven patients in group B were bridged to LTx; 6 of these patients (86%) had hypercarbia before lung reduction compared with 8 (40%) in group A (p < 0.05). All are alive after LTx: the forced expiratory volume in 1 second is 53% and the forced vital capacity is 64% of predicted. CONCLUSIONS: Lung reduction is safe and effective in selected LTx candidates with end-stage emphysema and has the potential to provide an alternative to LTx. Long-term follow-up is warranted to confirm these results.
RD Dowling, P Williams, M Zenati, BP Griffith, and RL Hardesty. 1995. “Infections and pathologic factors in the donor lung.” J Thorac Cardiovasc Surg, 109, 6, Pp. 1263-4.
M Zenati, RJ Keenan, RJ Landreneau, IL Paradis, PF Ferson, and BP Griffith. 1995. “Lung reduction as bridge to lung transplantation in pulmonary emphysema.” Ann Thorac Surg, 59, 6, Pp. 1581-3.Abstract
We present a case of bridging to lung transplantation by means of laser ablation of emphysematous bullae in a lung transplant candidate. The patient underwent successful left single-lung transplantation 17 months after lung reduction. He is now well 3 months after transplantation.
M Zenati, CL Madia, LA De Nino, and DN Payne. 1995. “Surgical management of mobile aortic atheroma diagnosed by intraoperative transesophageal echocardiography.” J Card Surg, 10, 5, Pp. 608-10.
U Livi, A Milano, U Bortolotti, R Casula, M Zenati, and D Casarotto. 1994. “Results of heart transplantation by extending recipient selection criteria.” J Cardiovasc Surg (Torino), 35, 5, Pp. 377-82.Abstract
From November 1985 to July 1993, 29 out of 241 patients (12%) who underwent heart transplantation (HTx) at our institution had one or more "classical" contraindications to HTx: age > or = 60 years (20 patients); insulin-dependent diabetes mellitus (5 patients); irreversible renal failure requiring combined heart-kidney transplantation (2 patients); previous surgery for malignancy (1 patient); familial hypercholesterolemia (1 patient) and active systemic infection (1 patient). The main indication for HTx was ischemic cardiomyopathy (21 patients, 61%). Immunosuppression regimen consisted of Cyclosporine and Azathioprine, oral prednisone being subsequently added in 6 patients because of persistent rejection. There were 2 perioperative deaths and one late death. Follow-up ranged from 1 to 88 months (mean, 28 +/- 20) with an actuarial survival at 5 years of 85 +/- 8%. Annual cardiac catheterization demonstrated normal graft function and coronary arteries in all. No significant differences in survival, incidence of rejection and infection, renal function and duration of hospitalization were found when these patients were compared with those with no contraindications to HTx. In conclusion, HTx can be performed with good early clinical results in selected patients with "classical" contraindications to HTx; longer follow-up, however, is needed to confirm whether extension of the recipient selection criteria justified.
M Zenati, A Milano, U Livi, A Cattelan, and D Casarotto. 1994. “Successful treatment of disseminated infection with Listeria monocytogenes in a heart transplant recipient.” J Heart Lung Transplant, 13, 2, Pp. 345-6.
A Milano, U Livi, R Casula, U Bortolotti, A Gambino, M Zenati, M Valente, A Angelini, G Thiene, and D Casarotto. 1993. “Influence of marginal donors on early results after heart transplantation.” Transplant Proc, 25, 6, Pp. 3158-9.
RD Dowling, M Zenati, SA Yousem, AW Pasculle, RL Kormos, JA Armitage, BP Griffith, and RL Hardesty. 1992. “Donor-transmitted pneumonia in experimental lung allografts. Successful prevention with donor antibiotic therapy.” J Thorac Cardiovasc Surg, 103, 4, Pp. 767-72.Abstract
Bacterial pneumonia is the most common cause of early morbidity and mortality (less than 2 weeks) after heart-lung transplantation. The majority (76%) of cultures taken from human donor tracheas at the time of explant grew bacteria. The abnormal immune response of the lung allograft and the common finding of bacterial contamination of lung donors led us to hypothesize that clinically silent bacterial contamination of the donor lung progresses to pneumonia in the recipient and that antibiotic treatment of donors will prevent the development of pneumonia in the recipient. Inocula of Streptococcus pneumoniae were instilled into the left middle lobe of normal and donor dogs to identify the number of bacteria that would result in pneumonia in a normal animal and the amount that, when given to a donor, would result in pneumonia in the recipient. Initial studies established that inocula of 10(4) colony-forming units of S. pneumoniae did not result in pneumonia in normal or immunosuppressed animals. When 10(4) colony-forming units or as few as 10(2) were instilled into the left middle lobe of donors 24 hours before explantation and use of the lung for transplantation, severe acute bronchopneumonia developed in all 18 recipients. Treatment of donors with aerosol and intravenous antibiotics, but not with either alone, prevented pneumonia in the recipients. We conclude that bacterial contamination of the donor lung leads to pneumonia in recipients. Intravenous and aerosol antibiotic treatment of donors with bacterial contamination prevents pneumonia in canine lung recipients. Treatment of human donors with this antibiotic regimen may decrease the prevalence of early bacterial pneumonia.
RJ Keenan, AJ Duncan, SA Yousem, M Zenati, M Schaper, RD Dowling, Y Alarie, GJ Burckart, and BP Griffith. 1992. “Improved immunosuppression with aerosolized cyclosporine in experimental pulmonary transplantation.” Transplantation, 53, 1, Pp. 20-5.Abstract
Rejection remains a major obstacle to long-term success of pulmonary transplantation. Direct delivery of cyclosporine to lung allografts may produce better control of rejection by generating high intragraft concentrations of drug with decreased systemic delivery and toxicity. The efficacy of inhaled cyclosporine in preventing allograft rejection was compared with systemic delivery by intramuscular injections in a rat model of lung transplantation (Brown-Norway to Lewis). Group 1 animals were given no immunosuppression. Group 2 received a single i.m. injection of 25 mg/kg CsA on the day of operation while group 3 received daily doses on postoperative days 0-3. Groups 4-7 received aerosolized CsA daily for seven days. The aerosol generator produced an airborne concentration of CsA of 180 mg/m3 with a mean particle size of 0.7 mu and estimated pulmonary depositions of CsA of 0.98-3.6 mg/kg/day. Animals were killed on POD 7, and the transplanted lungs graded histologically in a blinded fashion. All control animals showed destructive grade 4 changes by POD 7. Animals receiving high-dose aerosolized CsA (groups 6 and 7) showed minimal changes with a mean rejection grade of 1.3. A single i.m. dose of CsA (group 2) failed to prevent rejection; the mean grade was 2.2. Animals given four i.m. doses of CsA had a mean grade of 1.8. Aerosolized CsA provided significantly better control of rejection than did systemic CsA (groups 6 and 7 vs. groups 2 and 3; P less than 0.0002 and less than 0.0054, respectively). Local delivery of CsA by aerosol inhalation is effective in limiting acute rejection of the rat lung allograft.
M Zenati, F del Nonno, B Marino, and DC di Carlo. 1992. “Pulmonary atresia and intact ventricular septum associated with pulmonary artery sling.” J Thorac Cardiovasc Surg, 104, 6, Pp. 1755-6.
AJ Duncan, JS Dummer, IL Paradis, JH Dauber, SA Yousem, MA Zenati, RL Kormos, and BP Griffith. 1991. “Cytomegalovirus infection and survival in lung transplant recipients.” J Heart Lung Transplant, 10, 5 Pt 1, Pp. 638-44; discussion 645-6.Abstract
Fifty-nine patients who survived more than 30 days after lung transplantation (52 heart-lung, seven double lung, and two single lung) were studied for mortality and morbidity related to cytomegalovirus (CMV) infection. CMV infection developed in 32 patients (54%) and was more common in the preoperatively CMV seropositive group (95%) as compared with the seronegative group (38%). Symptomatic infections, pneumonitis, and CMV-related mortality, however, were higher in the seronegative (primary infection) group and actuarial survival was worse in these patients (40% and 23% at 1 and 5 years, respectively). Transplantation of CMV-seropositive donor organs was associated with a significantly higher incidence of primary infection and use of seronegative blood products led to a decrease in the primary CMV infection rate. The mortality of primary CMV infection was 54% and this was associated with a significantly higher rate of pulmonary superinfections in the first year after transplantation. The incidence of late pulmonary infections was associated with the development of chronic rejection rather than CMV status. We conclude that primary CMV infection has a major impact on the outcome after lung transplantation. The high mortality of primary infections justifies an aggressive approach to prevention and treatment in the at-risk seronegative group.