Randomized clinical trial of metronidazole ointment versus placebo in perianal Crohn's disease.

BACKGROUND: The potential for metronidazole 10 per cent ointment to exert therapeutic benefit in perianal Crohn's disease, while minimizing the adverse effects found with oral metronidazole, was evaluated in a randomized placebo-controlled study. METHODS: Subjects with perianal Crohn's disease were randomized to metronidazole 10 per cent ointment, 0.7 g applied perianally three times daily, or placebo ointment. The Perianal Crohn's Disease Activity Index (PCDAI) was scored at baseline and after 4 weeks of treatment. Perianal pain was assessed on a visual analogue scale. RESULTS: Seventy-four subjects (33 metronidazole, 41 placebo) were evaluated. The mean(s.e.m.) reduction in PCDAI score at 4 weeks was 2.4(0.5) in the metronidazole group and 2.2(0.4) in the placebo group (P = 0.660). More subjects in the metronidazole group than the placebo group showed a reduction in PCDAI score of at least 5 points (10 of 27 versus 4 of 34; P = 0.031). Perianal discharge was reduced significantly in metronidazole-treated subjects (P = 0.012). A greater reduction in perianal pain was seen in the metronidazole group, which approached statistical significance (P = 0.059). No serious adverse events were reported. CONCLUSION: Metronidazole 10 per cent ointment was not effective in the reduction of PDCAI score, but some secondary outcomes showed improvement suggestive of a treatment effect. It is well tolerated, with minimal adverse effects, and has potential as treatment for pain and discharge associated with perianal Crohn's disease. REGISTRATION NUMBER: NCT00509639 (http://www.clinicaltrials.gov).

As originally published in 1994: Simplified, standardized technique for cervical esophagogastric anastomosis. Updated in 2000.

Using transhiatal esophagectomy, the ease of performing the cervical esophagogastric anastomosis varies greatly depending on neck size, length of mobilized stomach, and adhesions from previous neck operations. We therefore have developed a technique, used in 45 consecutive patients undergoing transhiatal esophagectomy, that has simplified the technical performance of cervical esophagogastric anastomosis.

The left atrial appendage: our most lethal human attachment! Surgical implications.

OBJECTIVES: To prevent death from atrial fibrillation, a cardiac disease which kills by producing emboli. Atrial fibrillation causes about 25% of strokes and increases stroke rate by five times. Over 90% of these embolic strokes are from clots originating in the left atrial appendage. This study addresses the surgical feasibility of removing the appendage to prevent future deaths in two subcategories of patients. (1) Prophylactic removal during open-heart surgery to study its safety. Theoretically, as these patients age and some develop atrial fibrillation, protection from embolic strokes would already be present. (2) Therapeutic removal in chronic atrial fibrillation patients by means of a thorascopic approach. Its technical feasibility is demonstrated. Its actual stroke prevention potential awaits large studies. METHODS: Appendectomy has been evaluated three ways. (1) Experimentally, thorascopic appendage removal was performed on 20 goats with endoscopic approach. Late studies showed a cleanly healed atrial closure after stapling, and no puckering of tissue as seen with the purse-string approach. (2) Safety of human appendectomy was demonstrated in 437 patients (1995-1997). Routine appendectomy was performed during open-heart surgery. Forty-three appendages were stapled, 391 sutured off. (3) Thorascopic appendectomy in seven patients with chronic atrial fibrillation has been successfully accomplished as an isolated surgical procedure. Stapling or suture closure provides a much cleaner, non-puckered suture line than a purse string. RESULTS: In prophylactic removal, no acute bleeding occurred. No late problems have been identified. Endoscopic removal of the appendage has been successful in seven atrial fibrillation patients. CONCLUSIONS: The left atrial appendage is a lethal source of emboli in atrial fibrillation patients. As patients age and often develop atrial fibrillation, prophylactic appendage removal whenever the chest is open is suggested as a method to prevent future strokes. In chronic atrial fibrillation patients, appendectomy can be done with a mini-thorascopic approach. Further studies are planned to demonstrate the effectiveness of appendectomy in preventing strokes in the chronic fibrillating patients.

Omeprazole or ranitidine bismuth citrate triple therapy to treat Helicobacter pylori infection: a randomized, controlled trial in Vietnamese patients with duodenal ulcer.

AIM: To evaluate the effectiveness of triple therapy containing either omeprazole or ranitidine bismuth citrate (RBC) to treat H. pylori infection in Vietnamese duodenal ulcer patients. METHODS: Patients infected with H. pylori were randomized to receive either omeprazole (20 mg b.d.), clarithromycin (500 mg b.d.) and amoxycillin (1 g b.d.) for 10 days (OAC), or RBC (400 mg b.d.), clarithromycin (500 mg b.d.) and amoxycillin (1 g b.d.) for 10 days (RAC). H. pylori eradication and ulcer healing was established by a follow-up oesophagogastroduodenoscopy (EGD) at least 4 weeks after therapy. Side-effects and compliance were assessed. RESULTS: One hundred and four out of 108 (96%) patients with a duodenal ulcer were infected with H. pylori. Eighty per cent of infected patients had detectable CagA IgG antibodies. Fifty-seven patients received OAC and 47 received RAC. OAC eradicated H. pylori in 91 and 86% of patients by per protocol (PP) and intention-to-treat (ITT) analysis, respectively. PP and ITT eradication rates for RAC were 96 and 91%. Ulcer healing at the follow-up EGD was 89% with OAC and 100% with RAC. Side-effects were minor. No patient failed to complete the protocol due to side-effects. CONCLUSION: Triple therapy with either omeprazole or RBC is highly effective in eradicating H. pylori and healing duodenal ulcer in Vietnamese patients.

Astigmatic single photon emission computed tomography imaging with a displaced center of rotation.

A filtered backprojection algorithm is developed for single photon emission computed tomography (SPECT) imaging with an astigmatic collimator having a displaced center of rotation. The astigmatic collimator has two perpendicular focal lines, one that is parallel to the axis of rotation of the gamma camera and one that is perpendicular to this axis. Using SPECT simulations of projection data from a hot rod phantom and point source arrays, it is found that a lack of incorporation of the mechanical shift in the reconstruction algorithm causes errors and artifacts in reconstructed SPECT images. The collimator and acquisition parameters in the astigmatic reconstruction formula, which include focal lengths, radius of rotation, and mechanical shifts, are often partly unknown and can be determined using the projections of a point source at various projection angles. The accurate determination of these parameters by a least squares fitting technique using projection data from numerically simulated SPECT acquisitions is studied. These studies show that the accuracy of parameter determination is improved as the distance between the point source and the axis of rotation of the gamma camera is increased. The focal length of the focal line perpendicular to the axis of rotation is determined more accurately than the focal length to the focal line parallel to this axis.

Composite graft replacement of the aortic root in 335 patients with aneurysm or dissection.

The hypothesis that replacement of the aortic root with a valved composite graft is a safe and effective therapy for aneurysms involving the sino-tubular segment of the aorta was tested by a retrospective review. From September 1978 to January 1995, 335 consecutive patients underwent prosthetic aortic root replacement as the primary operation for aneurysm (222) or dissection (acute 59, chronic 54). There were 248 men (74%) and 87 women (26%) with a mean age of 50 +/- 14 years. 22 patients (6.6%) experienced hospital death primarily due to cardiac causes. Mortality was significantly higher in patients with acute dissection versus those with non-dissecting aneurysms and chronic dissection. Sex, Marfan syndrome (20.3% of patients), mitral regurgitation, coronary artery disease, and era of operation had no effect on early outcome. Mortality was significantly increased in patients aged over 50 years, in those with circulatory compromise, and in patients requiring emergency operation. Follow-up was complete in 313 survivors (97%) at a mean of 61.3 +/- 44 months. Actuarial survival was 80% at 5 and 67% at 10 years. There were no complications involving the coronary anastomoses, other than infection-related, regardless of the mode of ostial reattachment.

Effect of registration errors between transmission and emission scans on a SPECT system using sequential scanning.

UNLABELLED: The purpose of this study was to evaluate the effects of patient motion on nonuniform attenuation correction of cardiac SPECT when the transmission and emission scans were performed sequentially. By using a sequential protocol rather than doing the scans simultaneously, contamination from the emission scan into the transmission scan could be eliminated, but registration of the two scans become a concern. METHODS: Transmission and emission scans were acquired using both an anthropomorphic thorax phantom containing a cardiac insert and a human volunteer. The types of motion considered were transverse shifts, axial shifts and rotations that occur in the time period between the transmission and emission scan. For this study, the various types of motion were simulated in the data. Both the transmission and emission data were reconstructed using filtered backprojection. A single-iteration Chang algorithm, modified for nonuniform attenuation correction, was used to further process the emission data. To evaluate the effects of motion errors, circumferential profiles, all normalized to the same scale, were generated for each case. The cardiac images reconstructed using registered data were considered references. Error profiles were generated by subtracting misaligned images from the reference and then normalizing the difference by the reference. For comparison purposes, an error profile was generated for the case in which no attenuation correction was performed. RESULTS: It was found that, for transverse and axial shifts of 2.9 cm, the normalized myocardial SPECT activity was decreased in certain regions of the heart by 20%-35%. For a 12 degrees rotational shift, the error was on the order of 10%-20%, compared to a normalized variation of 20%-25% in the image with no attenuation correction. CONCLUSION: The results indicate that registration errors of 2-3 cm can seriously affect image quality in both the phantom and human images.

Immunohistochemical abnormalities of fibrillin in cardiovascular tissues in Marfan's syndrome.

BACKGROUND: Molecular defects in the glycoprotein fibrillin are believed to be responsible for impaired structural integrity of cardiovascular, skeletal, and ocular tissues in Marfan's syndrome (MFS). Traditionally, excellent results have been achieved with the Bentall composite graft repair of aneurysms of the ascending aorta in MFS. However, because of the potential complications associated with prosthetic valves, there is growing interest in techniques that preserve the native aortic valve. METHODS: Between May 1994 and February 1995, 15 patients with a history of concomitant or remote aortic root aneurysms or dissection underwent operation for valvular heart disease. Specimens of aortic valve, ascending aortic wall, and mitral valve were obtained specifically to observe differences in fibrillin content and architecture between patients with (n = 9) and without (n = 6) MFS. In addition, control specimens of aortic valve, aortic wall, and mitral valve were obtained from 4 patients with isolated valvular or coronary artery disease but no evidence of connective tissue disorders or other aortic pathologic conditions. Fibrillin immunostaining using indirect immunofluorescence was used. Specimens were coded and graded by a blinded observer to determine quantity, homogeneity, and fragmentation of fibrillin. RESULTS: Observed fibrillin abnormalities in MFS and control patients were limited to the midportion (elastin-associated microfibrils) of the aortic valve, aortic wall, and mitral valve tissues. Fibrillin abnormalities of aortic valve, aortic wall, and mitral valve tissues were seen in all patients with MFS and were most severe in those older than 20 years. Similar fibrillin abnormalities of aortic valve and aortic wall specimens were observed in control patients more than 60 years old. CONCLUSIONS: Even in the setting of a normal-appearing aortic valve, the current rationale for widespread use of valve-sparing repairs of aortic root aneurysms in patients with MFS and patients older than 60 years should be carefully reexamined in light of these findings.

cGMP accumulation and gene expression of soluble guanylate cyclase in human vascular tissue.

Gene expression of soluble guanylate cyclase (sGC) and cGMP accumulation in response to sodium nitroprusside (SNP) were studied in cultured human vascular cells and freshly harvested vascular tissue. As revealed by reverse transcriptase-polymerase chain reaction, cultured smooth muscle and endothelial cells, as well as freshly isolated human vascular tissue, express mRNA for the alpha 3 and beta 3 subunits but not for the alpha 2 and beta 3 subunits is evident even in the absence of increased cGMP accumulation in response to SNP. cGMP accumulation in human cells cultured from different vascular beds typically increased two- to five-fold (maximum of 11.4-fold) over baseline following stimulation with 100 microM SNP. Bovine, murine, canine, and avian vascular smooth muscle cells accumulated similar or lower amounts of cGMP than human cells, whereas porcine, rat, and rabbit smooth muscle cells accumulated greater amounts of cGMP. In freshly harvested human vessels, cGMP accumulation in response to SNP was found to increase fifteen-fold over baseline. In contrast to the SNP-induced cGMP accumulation, cGMP levels in response to particulate guanylate cyclase activator atriopeptin II were equal to or greater in cultured human cells than in fresh human vascular tissue. We conclude that human vascular cells (fresh and cultured) express the mRNA for both a large (alpha 3) and a small (beta 3) sGC subunit and that fresh human cells are more sensitive to SNP stimulation.

The Marfan syndrome and the cardiovascular surgeon.

The authors present the current status of surgery for the cardiovascular manifestations of the Marfan syndrome. In addition, a brief review of current Marfan genetic research is presented. Data on all Marfan patients undergoing aortic root replacement at the Johns Hopkins Hospital (September 1976-June 1995) were analyzed. Survival and event-free curves were calculated and risk factors for early and late death were determined by univariate and multivariate analysis. Two hundred twelve Marfan patients underwent aortic root replacement using composite graft (202), homograft (8) or valve-sparing procedures (2). One hundred eighty-five patients underwent elective repair with no 30-day mortality. Twenty-seven patients underwent urgent surgery, primarily for acute dissection; two patients with aortic rupture died in the operating room. Actuarial survival of the 212 patients was 88% at 5 years, 78% at 10 years and 71% at 14 years. By multivariate analysis, only poor NYHA class, male gender and urgent surgery emerged as significant independent predictors of early or late mortality. Histologic examination of excised Marfan aortic leaflets by immunofluorescent staining for fibrillin showed fragmentation of elastin-associated microfibrils. These studies suggest cautious use of valve-sparing procedures in Marfan patients. Over the last 5 years significant progress has been made in identifying mutant genes that code for defective fibrillin microfibrils in Marfan patients. Attempts are underway to develop animal models of Marfan disease for study of possible gene therapy. Aortic root replacement can be performed in Marfan patients with operative risk under 5%. Long-term results are gratifying. At present, valve-sparing procedures should be used cautiously in Marfan patients because of fibrillin abnormalities in the preserved aortic valve leaflets.

Aortic root replacement. Risk factor analysis of a seventeen-year experience with 270 patients.

Between September 1976 and September 1993, 270 patients underwent aortic root replacement at our institution. Two hundred fifty-two patients underwent a Bentall composite graft repair and 18 patients received a cryopreserved homograft aortic root. One hundred eighty-seven patients had a Marfan aneurysm of the ascending aorta (41 with dissection) and 53 patients had an aneurysm resulting from nonspecific medial degeneration (17 with dissection). These 240 patients were considered to have annuloaortic ectasia. Thirty patients were operated on for miscellaneous lesions of the aortic root. Thirty-day mortality for the overall series of 270 patients was 4.8% (13/270). There was no 30-day mortality among 182 patients undergoing elective root replacement for annuloaortic ectasia without dissection. Thirty-six of the 270 patients having root replacement also had mitral valve operations. There was no hospital mortality for aortic root replacement in these 36 patients, but there were seven late deaths. Twenty-two patients received a cryopreserved homograft aortic root; 18 of these were primary root replacements and four were repeat root replacements for late endocarditis. One early death and two late deaths occurred in this group. Actuarial survival for the overall group of 270 patients was 73% at 10 years. In a multivariate analysis, only poor New Year Heart Association class (III and IV), non-Marfan status, preoperative dissection, and male gender emerged as significant predictors of early or late death. Endocarditis was the most common late complication (14 of 256 hospital survivors) and was optimally treated by root replacement with a cryopreserved aortic homograft. Late problems with the part of the aorta not operated on occur with moderate frequency; careful follow-up of the distal aorta is critical to long-term survival.

Composite graft repair of Marfan aneurysm of the ascending aorta: results in 150 patients.

One hundred fifty consecutive Marfan patients undergoing composite graft repair of an ascending aorta aneurysm are reported. Twenty-six of the 150 patients had a preoperative dissection of the ascending aorta. There were no early deaths among 138 patients undergoing elective composite graft repair. There was one early death among 12 patients undergoing urgent operation; this patient arrived at the hospital with a rupturing aneurysm. Twenty-four of the 150 patients had mitral procedures; there were no early deaths in this group. There have been 14 late deaths among the 149 hospital survivors (9%). Actuarial survival of 150 patients at 1, 5, 10, and 14 years was 93%, 92%, 81%, and 73% respectively. Risk factors for early or late death were identified by multivariate analysis and only New York Heart Association class (III or IV) and male gender emerged as significant independent predictors of mortality. Late complications directly related to the composite graft have been gratifyingly low; only 2 patients had coronary dehiscence and 3 had thromboembolic events. Endocarditis emerged as an important late complication in 8 patients (5%). Two patients were successfully treated with antibiotics, 3 died before widespread availability of cryopreserved homografts, and 3 patients treated with antibiotics and homograft root replacement have had no evidence of recurrent infection. Seven patients with dissection in this series had aortic diameters of 6.5 cm or less. This experience supports the concept that composite graft repair in Marfan patients is mandated when the aneurysm reaches 5.5 to 6 cm, even in the asymptomatic patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Simplified, standardized technique for cervical esophagogastric anastomosis.

Using transhiatal esophagectomy, the ease of performing the cervical esophagogastric anastomosis varies greatly depending on neck size, length of mobilized stomach, and adhesions from previous neck operations. We therefore have developed a technique, used in 45 consecutive patients undergoing transhiatal esophagectomy, that has simplified the technical performance of cervical esophagogastric anastomosis.

Single-stage repair of distal aortic arch and thoracoabdominal dissecting aneurysms using aortic tailoring and circulatory arrest.

The adjuncts of profound hypothermic circulatory arrest and aortic tailoring are combined with standard graft replacement of the noncritical portions of the aorta. This combination permits single-stage replacement of the arch, thoracic, and abdominal aorta in patients with postdissection aneurysm. Reconstruction is begun with repair of the mid to distal aortic arch and Dacron graft replacement of the proximal descending thoracic aorta, usually under profound hypothermic circulatory arrest. The proximal graft is then cannulated and the patient partially warmed while the middle segment is "tailored." Aortic tailoring consists of longitudinal aortotomy and removal of the dissection membrane(s) from the distal third of the descending thoracic aorta to below the renal arteries. The aorta is then closed creating a single channel 2 to 3 cm in diameter and containing the origins of the important intercostal, lumbar, and visceral arteries. A Dacron graft is used to replace the infrarenal segment. Five patients have successfully undergone single-stage, total repair of the aorta including the arch, thoracic, and abdominal segments. All survival without paraplegia or significant visceral ischemia. Follow-up has not shown dilatation of the tailored segment. We believe that reduction in diameter of the tailored aortic segment and thus wall tension, growth of neointima on all luminal aortic surfaces, and active collagen deposition contribute to the success of this procedure.

Operative treatment of pediatric obstructive hypertrophic cardiomyopathy: a 26-year experience.

We retrospectively reviewed the 26-year National Institutes of Health experience with operative treatment of obstructive hypertrophic cardiomyopathy in pediatric patients. Operative criteria were either severe obstructive symptoms (New York Heart Association functional class III or IV) or sudden death. Seventeen patients underwent 19 open procedures, of which the present study is comprised. Complete follow-up was available 10.1 +/- 1.4 years (mean +/- standard error; range, 0.8 to 26.2 years) after operation. The mean ages at diagnosis and operation were 11.9 +/- 1.3 years (range, 1 to 17 years) and 14.8 +/- 0.7 years (range, 9 to 17 years), respectively. The preoperative intraventricular septum mean dimension was 23.2 +/- 1.3 mm (range, 11 to 36 mm). The left ventricular outflow tract gradient was 74 +/- 9 mm Hg (range, 20 to 175 mm Hg) at rest and 94 +/- 7 mm Hg (range, 55 to 175 mm Hg) with provocation. Fifteen patients (88%) underwent left ventricular myotomy and myectomy, and 2 underwent mitral valve replacement. Two patients who initially received left ventricular myotomy and myectomy later underwent mitral valve replacement. There were one perioperative death (6%) and five late sudden deaths (31%) at 3.8, 8.7, 9.6, 14.1, and 21 years postoperatively. Kaplan-Meier survival was 86% +/- 8% at 5 years and 77% +/- 12% at 10 years. After operation, the left ventricular outflow tract gradient decreased almost 80% to 21 +/- 15 mm Hg (p = 0.0001). In 8 patients, the left ventricular outflow tract gradient completely resolved.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular function in experimental mitral regurgitation with intact chordae tendineae.

Left ventricular function in mitral regurgitation has typically been studied in models that either sever the chordae tendineae or create a ventriculoatrial shunt. These methods may have adverse effects on left ventricular function independent of the regurgitant lesion. An animal model of chronic mitral regurgitation was therefore developed that both preserves annuloventricular continuity and avoids the use of external shunts. A circular 0.16 to 0.24 mm/kg defect was created in the anterior mitral valve leaflet of weanling sheep under direct vision with the aid of cardiopulmonary bypass. Six animals were studied preoperatively and immediately postoperatively (acute regurgitation group), and 20 animals were studied 8.1 +/- 0.2 (mean +/- one standard deviation) months postoperatively (chronic regurgitation group). Animals with chronic mitral regurgitation were compared with an age- and weight-matched control group that was not operated on (n = 7). Volumetric data and ejection fraction were derived from digitalized cineangiographic images. Maximal elastance was calculated from pressure-volume loops obtained from the simultaneous recording of left ventricular pressure by micromanometer-tipped left ventricular catheters, and volumes were obtained from digitalized images of epicardial echocardiographic recordings. Mitral valve perforation resulted in 3+ to 4+ mitral regurgitation and a calculated regurgitant fraction of 37% +/- 7% (mean +/- one standard deviation). Acute mitral regurgitation was associated with an increase in left ventricular end-diastolic volume from 110 +/- 17 to 121 +/- 23 ml (p < or = 0.05) and no change in end-systolic volume. These changes were associated with an increase in fractional shortening, from 29% +/- 11% to 40% +/- 10% (p < or = 0.05), and an increase in velocity of circumferential shortening, from 1.5 +/- 0.7 to 2.9 +/- 0.7 circ/sec (p < or = 0.05). However, there was no change in maximal elastance, a load-independent index of left ventricular function. Conversely, animals with chronic mitral regurgitation exhibited an elevated end-diastolic volume (202 +/- 32 versus 145 +/- 34, p < or = 0.05), an elevated end-systolic volume (104 +/- 17 versus 63 +/- 20 ml, p < or = 0.05), and a reduced ejection fraction (48% +/- 6% versus 57% +/- 9%, p < or = 0.05) compared with controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Use of yttrium-90-labeled anti-Tac antibody in primate xenograft transplantation.

The high-affinity interleukin-2 receptor (IL-2R) is expressed by T cells activated in response to foreign histocompatibility antigens but not by normal resting cells. Thus, blockade of the interaction of IL-2 with its receptor could achieve selective immunosuppression. Accordingly, anti-Tac, a murine IgG2a class monoclonal antibody specific to the IL-2R, was used alone or in a chelated form with yttrium-90 (90Y), a pure beta emitter, to inhibit rejection of cardiac xenografts from Macaca fascicularis (cynomolgus) donors transplanted to the cervical or abdominal region of Macaca mulatta (rhesus) recipients (n = 20). Animals received no immunosuppression (n = 3, group I, controls), unmodified anti-Tac (n = 5, 2 mg/kg q.o.d., group II), or 90Y-anti-Tac (n = 5, 16 mCi, group III). To distinguish the nonspecific immunosuppressive effect of radiation, 90Y was administered bound to UPC-10 (n = 4, 16 mCi, group IV), another murine monoclonal antibody that does not specifically recognize activated immunoresponsive cells. All immunosuppression was administered in divided doses during the first 2 weeks posttransplant. Group I animals rejected their grafts at 6.7 +/- 1 days and demonstrated a rise in soluble IL-2R levels at the time of rejection, indicating the generation of Tac-expressing and -releasing cells. Graft survival in group II was not prolonged compared with controls (mean survival 6.2 +/- 1 days; P greater than 0.05). In contrast, graft survival in animals that received the designed dosage of 90Y-anti-Tac was significantly prolonged to an average of 38.4 +/- 5 days compared with groups I and II (P less than 0.005 and P les sthan 0.0005, respectively). Prolongation of graft survival occurred in animals that received 90Y-UPC-10 (mean survival 21.3 +/- 5 days, P less than 0.05 versus group I, P less than 0.01 versus group II). However, 90Y-UPC-10 was significantly less effective in prolonging graft survival than 90Y-anti-Tac, in which one-half the per-kilogram dosage of radioactivity was delivered in specific fashion via anti-Tac (P less than 0.025). Reversible nonlethal bone marrow suppression occurred without associated nephro- or hepatotoxicity, and virtually all animals developed antibodies to the murine monoclonal. Thus, the approach used in the present study, IL-2R-directed therapy with 90Y-anti-Tac, may have potential applications in organ transplantation and in the treatment of Tac-expressing neoplastic diseases.