The StarClose Vascular Closure System: interventional results from the CLIP study.

BACKGROUND: The StarClose Vascular Closure System is a femoral access site closure technology that uses a flexible nitinol clip to complete a circumferential, extravascular arteriotomy close. The Clip CLosure In Percutaneous Procedures study was initiated to study the safety and efficacy of the StarClose device in subjects undergoing diagnostic and interventional catheterization procedures. METHODS: A total of 17 U.S. sites enrolled 596 subjects, with 483 subjects randomized at a 2:1 ratio to receive StarClose or standard compression of the arteriotomy after the percutaneous procedure. The study included roll-in (n = 113), diagnostic (n = 208), and interventional (n = 275) arms with a primary safety endpoint of major vascular complications through 30 days and a primary efficacy endpoint of postprocedure time to hemostasis. RESULTS: The results of the diagnostic StarClose cohort have been reported separately. Results for the interventional arm revealed major vascular complications occurring in 1.1% of StarClose subjects (2/184) and 1.1% in manual compression subjects (1/91; P = 1.00). No infections were seen in either cohort. Minor complications in the StarClose interventional group occurred at a rate of 4.3% (8/184) and with compression at 9.9% (9/91; P = 0.107). Pseudoaneurysm or arteriovenous fistula was not seen with StarClose. With StarClose, procedural success was 100% (136/136) for the diagnostic group and 98.9% (181/183) in the interventional group. Device success for the treatment group was 86.8%. In the interventional cohort, 87.3% (158/181) of StarClose subjects reported a pain scale of 0-3 compared with 93.3% (84/90) in the compression group, which was not statistically different. CONCLUSIONS: The clinical results of this study demonstrate that the StarClose Vascular Closure System is noninferior to manual compression with respect to the primary safety endpoint of major vascular events in subjects who undergo percutaneous interventional procedures. StarClose significantly reduced time to hemostasis, ambulation, and dischargeability when compared with compression.

The safety and efficacy of the StarClose Vascular Closure System: the ultrasound substudy of the CLIP study.

BACKGROUND: The StarClose Vascular Closure System (Abbott Vascular, Redwood City, CA) features a nitinol clip that is designed to achieve closure of the femoral arteriotomy access site. The CLIP Study was performed to assess the safety and efficacy of StarClose when compared with standard manual compression following 5-6 French diagnostic or interventional percutaneous procedures. A substudy of this trial was designed to assess the utility of duplex ultrasonography to assess patency of the femoral artery and to determine access site complications (pseudoaneurysm, arteriovenous fistula, hematoma, deep vein thrombosis) in a multicenter prospective trial. This is the report of the duplex ultrasound (DUS) substudy of the CLIP trial. METHODS: A total of 17 U.S. sites enrolled 596 subjects with 483 subjects randomized at a 2:1 ratio to receive StarClose or manual compression of the arteriotomy after a percutaneous procedure. The study included roll-in (n = 113), diagnostic (n = 208), and interventional (n = 275) arms with a primary safety endpoint of major vascular complications through 30 days and a primary efficacy endpoint of postprocedure time to hemostasis. A substudy of the CLIP interventional arm evaluated DUS images of the closure site at five study sites, targeting 100 subjects at day 30 following hemostasis. The DUS protocol was devised and implemented by an independent vascular ultrasound core laboratory with extensive experience in vascular device trials. DUS inguinal region from 6 cm proximal to 6 cm distal to the arteriotomy puncture was performed. A qualitative examination was performed to determine the presence of iatrogenic vascular injuries: hematoma, pseudoaneurysm (PSA), arteriovenous fistula (AVF), and arterial/venous thrombosis or stenosis using 2-dimensional gray scale, color, and focused Doppler images. RESULTS: DUS of 96 subjects randomized to StarClose (n = 71) and compression (n = 25) were performed and evaluated. There was no evidence of hematoma, PSA, or AVF observed in the StarClose group. No StarClose subjects in the substudy had a PSA or AVF. All patients in the substudy demonstrated patency of the access site artery and vein without thrombosis or stenosis. Finally, in the entire study cohort, no clinically-driven DUS studies demonstrated iatrogenic vascular injury or vessel thrombosis in the StarClose treated patients. CONCLUSION: DUS, a safe and reliable method for determining the safety and efficacy of access site closure devices, is a reliable, safe, inexpensive and accurate method of assessing vascular access site complications in multicenter trials. In this substudy of the CLIP study, DUS found no statistical difference in access site complications between the StarClose and manual compression groups. Both groups maintained vessel patency without stenosis, thrombosis, hematoma, pseudoaneurysm, or AV fistula.

Percutaneous coronary intervention: current perspective.

More than 20 years have passed since percutaneous transluminal coronary angioplasty (PTCA) was introduced for the treatment of coronary artery disease. During the first decade, PTCA outcome had improved significantly. However, acute occlusive complications and restenosis remained as significant limitations of the procedure. During the second decade, new procedures, such as stents and atherectomy (directional coronary atherectomy, and Rotablator) had been introduced and had a significant impact on the outcome of percutaneous coronary intervention (PCI). In addition to the improvements in the equipment, the use of glycoprotein IIb/IIIa inhibitors to prevent platelet aggregation has reduced procedure-related complications. PCI continues to evolve with new developments such as distal protection devices to prevent distal embolism, brachytherapy and drug-eluting stents to prevent restenosis. These new technologies may play a significant role in expanding the applications of PCI in the future.

Replication in restenotic atherectomy tissue.

Previously, we demonstrated that replication in restenotic coronary atherectomy specimens was an infrequent and modest event. In general, this data was interpreted with caution, as immunocytochemistry for the proliferating cell nuclear antigen (PCNA) was used to subjectively assess proliferation and most of the tissue specimens were resected more than 3 months after the initial interventional procedure. The purpose of the present study was to use a more sensitive method of detecting replication, in situ hybridization for histone 3 (H3) mRNA, to determine the replication profile of human directional atherectomy specimens. Restenotic directional coronary atherectomy specimens from lesions that had undergone an interventional procedure within the preceding 3 months were studied. In addition, larger atherectomy specimens from peripheral arterial lesions were assessed to ensure that pockets of replication were not being overlooked in the smaller coronary specimens. We found evidence for replication in tissue resected from 2/17 coronary and 9/12 peripheral artery restenotic lesions. In contrast, 3/11 specimens resected from primary lesions of peripheral arteries also expressed H3 mRNA. We estimated that the maximum percentage of cells that were replicating in restenotic coronary, restenotic peripheral and primary peripheral artery tissue slides to be <0.5, < or =1.2 and <0.01%, respectively. Replication was found in tissue specimens resected both early and late after a previous interventional procedure. For specimens with >15 replicating cells per slide we found high levels of focal replication. Therefore, cell replication, as assessed by the expression of H3 mRNA, was infrequent in restenotic coronary artery specimens, whereas peripheral restenotic lesions had more frequent and higher levels of replication regardless of the interval from the previous interventional procedure. For all specimens the percentage of cells that were replicating was low, however focal areas with relatively high replication indices were presented. Although replication was more abundant in restenotic lesions it does not appear to be a dominant event in the pathophysiology of restenosis.

Suture-mediated closure of the femoral access site after cardiac catheterization: results of the suture to ambulate aNd discharge (STAND I and STAND II) trials.

Despite advances in other aspects of cardiac catheterization, manual or mechanical compression followed by 4 to 8 hours of bed rest remains the mainstay of postprocedural femoral access site management. Suture-mediated closure may prove to be an effective alternative, offering earlier sheath removal and ambulation, and potentially a reduction in hemorrhagic complications. The Suture To Ambulate aNd Discharge trial (STAND I) evaluated the 6Fr Techstar device in 200 patients undergoing diagnostic procedures, with successful hemostasis achieved in 99% of patients (94% with suture closure only) in a median of 13 minutes, and 1% major complications. STAND II randomized 515 patients undergoing diagnostic or interventional procedures to use of the 8Fr or 10Fr Prostar-Plus device versus traditional compression. Successful suture-mediated hemostasis was achieved in 97.6% of patients (91.2% by the device alone) compared with 98.9% of patients with compression (p = NS). Major complication rates were 2.4% and 1.1%, and met the Blackwelder's test for equivalency (p <0.05). Median time to hemostasis (19 vs 243 minutes, p <0.01) and time to ambulation (3.9 vs 14.8 hours, p <0.01) were significantly shorter for suture-mediated closure. Suture-mediated closure of the arterial puncture site thus affords reliable immediate hemostasis and shortens the time to ambulation without significantly increasing the risk of local complications.

Effects of adjunctive balloon angioplasty after intravascular ultrasound-guided optimal directional coronary atherectomy: the result of Adjunctive Balloon Angioplasty After Coronary Atherectomy Study (ABACAS).

OBJECTIVES: This study was conducted to evaluate: 1) the effect of adjunctive percutaneous transluminal coronary angioplasty (PTCA) after directional coronary atherectomy (DCA) compared with stand-alone DCA, and 2) the outcome of intravascular ultrasound (IVUS)-guided aggressive DCA. BACKGROUND: It has been shown that optimal angiographic results after coronary interventions are associated with a lower incidence ofrestenosis. Adjunctive PTCA after DCA improves the acute angiographic outcome; however, long-term benefits of adjunctive PTCA have not been established. METHODS: Out of 225 patients who underwent IVUS-guided DCA, angiographically optimal debulking was achieved in 214 patients, then theywere randomized to either no further treatment or to added PTCA. RESULTS: Postprocedural quantitative angiographic analysis demonstrated an improved minimum luminal diameter (2.88 +/- 0.48 vs. 2.6 +/- 0.51 mm; p = 0.006) and a less residual stenosis (10.8% vs.15%; p = 0.009) in the adjunctive PTCA group. Quantitative ultrasound analysis showed a larger minimum luminal diameter (3.26 +/- 0.48 vs. 3.04 +/- 0.5 mm; p < 0.001) and lower residual plaque mass in the adjunctive PTCA group (42.6% vs. 45.6%; p < 0.001). Despite the improved acute findings in the adjunctive PTCA group, six-month angiographic and clinical results were not different. The restenosis rate (adjunctive PTCA 23.6%, DCA alone 19.6%; p = ns) and target lesion revascularization rate (20.6% vs. 15.2%; p = ns) did not differ between the groups. CONCLUSIONS: With IVUS guidance, aggressive DCA can safely achieve optimal angiographic results with low residual plaque mass, and this was associated with a low restenosis rate. Although adjunctive PTCA after optimal DCA improved the acute quantitative coronary angiography and quantitative coronary ultrasonography outcomes, its benefit was not maintained at six months.

[A case of leiomyosarcoma of the jejunum with postoperative hepatic encephalopathy].

We report a case of leiomyosarcoma of the jejunum with postoperative hepatic encephalopathy. A 60-year-old man was operated for tumor of the abdomen. He was diagnosed as leiomyosarcoma of the jejunum with disseminated peritoneal metastasis, but no liver metastasis and cirrhosis. A palliative resection of the jejunum was performed. After operation, disturbance of orientation and apraxia with electroencepharographic abnormality and hyperammonemia developed. He was diagnosed as hepatic encephalopathy without lesion of the liver, and died 11 months after surgery. We consider that the portosystemic shunt and bleeding from the digestive tract due to invasion of metastatic lesions caused hepatic encephalopathy.

[Allogeneic bone marrow transplantation in children from related donors other than HLA-identical siblings].

Thirty-five children with poor-prognosis disease underwent allogeneic bone marrow transplantation (BMT) from related donors other than HLA identical siblings (parents in 18 cases, non-identical siblings in 14, and other relatives in 3). Phenotypically identical donors were involved in 12 cases, donors with one mismatched locus in 17, and donors with two or more mismatched loci in 6. Thirty-two of the children received total-body irradiation as part of their conditioning regimen, followed by unpurged marrow-cell infusions (averaging 4.09 x 10(8) cells/kg). Methotrexate and cyclosporin were administered for graft-versus-host disease (GVHD) prophylaxis; 15 of the children also received antithymocyte globulin (ATG) infusions. The effective graft rate for the group was 84. 8%; of 5 patients who experienced rejections, 4 had non-malignant diseases. The incidence of grade II-IV acute GVHD was 48.4%, significantly higher than that for groups that received allogeneic BMT from matched sibling donors. Three children (8.8%) died of severe GVHD. The incidence of acute GVHD in phenotypically matched patients was the same as that in the one-locus mismatched cases. MLC reactivity affected the incidence of acute GVHD (60.0% MLC-positive, 28.6% negative). ATG reduced the severity of acute GVHD. The event-free survival rate was 40.8 +/- 8.5% for the entire group (N = 35; 32.9 +/- 10.5% for the 22 children with malignancies, and 53.8 +/- 13.8% for the 13 with non-malignant diseases). Despite the risk of severe GVHD, allogeneic BMT from related donors other than HLA-identical siblings seems to be an effective treatment for patients with poor-prognosis diseases.

Remodeling after directional coronary atherectomy (with and without adjunct percutaneous transluminal coronary angioplasty): a serial angiographic and intravascular ultrasound analysis from the Optimal Atherectomy Restenosis Study.

OBJECTIVES: The intravascular ultrasound (IVUS) substudy of OARS (Optimal Atherectomy Restenosis Study) was designed to assess the mechanisms of restenosis after directional coronary atherectomy (DCA). BACKGROUND: Recent serial IVUS studies have indicated that late lumen loss after interventional procedures was determined primarily by the direction and magnitude of arterial remodeling, not by cellular proliferation. METHODS: Complete quantitative coronary angiography (QCA) and IVUS were obtained in 104 patients before and after intervention and during follow-up. All studies were performed after administration of 200 microg of intracoronary nitroglycerin. Angiographic measurements included minimum lumen diameter (MLD), interpolated reference diameter and diameter stenosis (DS). Intravascular ultrasound measurements included lesion and reference external elastic membrane (EEM), lumen and plaque+media cross-sectional area (CSA). The axial location of the lesion site was at the smallest follow-up lumen CSA; the reference segment was the most normal-looking cross section within 10 mm proximal to the lesion but distal to any major side branch. Results are reported as mean +/- one standard deviation. RESULTS: The QCA reference decreased from 3.51 +/- 0.46 mm to 3.22 +/- 0.44 mm; the MLD decreased from 3.22 +/- 0.47 mm to 2.03 +/- 0.72 mm; and the DS increased from 8 +/- 10% to 38 +/- 20%. On IVUS, the decrease in lumen CSA (from 8.8 +/- 2.5 mm2 to 5.5 +/- 4.0 mm2) was associated with a significant decrease in EEM (from 19.7 +/- 5.6 mm2 to 16.9 +/- 6.2 mm2); there was no significant increase in P+M (from 10.9 +/- 4.2 mm2 to 11.3 +/- 3.9 mm2). A change in lumen correlated with a change in EEM (r = 0.790, p < 0.0001), not with a change in P+M (r = 0.133, p = 0.2258). A decrease in reference EEM (from 19.1 +/- 7.7 mm2 to 17.6 +/- 8.0 mm2) also correlated with a decrease in lesion EEM (r = 0.665, p < 0.0001). Results in restenotic lesions were similar. CONCLUSION: Restenosis after optimal DCA is caused primarily by a decrease in EEM CSA that extends into contiguous reference segments.

Successful predilation of a resistant, heavily calcified lesion with cutting balloon for coronary stenting: a case report.

A 65-year-old man with a restenotic lesion of the mid LAD was scheduled for Wiktor stent placement. The IVUS revealed circumferential severe calcification. Two conventional, non-compliant angioplasty balloons inflated to high pressures failed to achieved sufficient dilatation and both ruptured. At this point, we selected high pressure inflation of the Cutting Balloon. The Cutting Balloon achieved adequate dilation for stenting and proved to be useful in predilating a circumferential, heavily calcified lesion.

Favorable strategy for the ostial lesion of the left anterior descending coronary artery: influence on narrowing of circumflex coronary artery.

We examined the effectiveness of Palmaz-Schatz (P-S) stent and directional coronary atherectomy (DCA) in ostial lesions of left anterior descending arteries (LAD). The P-S stent was implanted in 11 cases at LAD ostial lesions, and DCA was performed in 13 cases. Percent stenosis and vessel diameter at the target site and the ostium of the circumflex coronary artery (LCX) were measured before and after the procedure. The initial success rate was 100% in both groups. No major complication occurred. LAD ostial lesions were improved from 81.3+/-3.4% to -8.1+/-5.7% by P-S stent and from 82.8+/-2.6% to -2.7+/-3.9% by DCA. LCX ostial vessel diameter was not changed by DCA (from 3.0+/-0.2 mm to 3.1+/-0.3 mm); however, it was significantly decreased by P-S stent (from 2.9+/-0.2 mm to 2.6+/-0.2 mm, P < 0.01). When the angle of LAD and LCX was < or = 80 degrees from the view of RAO 30 degrees and Caudal 30 degrees, the LCX ostium was significantly narrowed by stenting at LAD ostium (P < 0.01). These findings indicate that both the P-S stent and DCA are effective and safe therapies for LAD ostial lesions in cases with LAD-LCX angle > 80 degrees. In cases with LAD-LCX angle < or = 80 degrees, however, DCA is a favored therapy rather than P-S stenting to avoid narrowing of the LCX ostium.

'Optimal' directional coronary atherectomy: final results of the Optimal Atherectomy Restenosis Study (OARS).

BACKGROUND: Previous clinical trials of directional coronary atherectomy (DCA) have failed to show significant improvement in early or late outcomes compared with balloon angioplasty (PTCA). The present study tested the hypothesis that more aggressive "optimal" atherectomy could be performed safely to produce larger initial lumen diameters and a lower late restenosis rate. METHODS AND RESULTS: The present study was a prospective multicenter registry of consecutive patients undergoing optimal DCA of de novo or restenotic lesions in 3.0- to 4.5-mm native coronary arteries. Optimal DCA was defined as using a 7F atherectomy device and adjunctive PTCA if necessary to achieve a < 15% residual stenosis. Six-month angiographic and 1-year clinical follow-up was planned in all patients. A total of 199 patients with 213 lesions met eligibility criteria for enrollment. Short-term procedural success was achieved in 97.5%, with a major complication rate (death, emergency bypass surgery, or Q-wave myocardial infarction [MI]) of 2.5%. There were no early deaths. Non-Q-wave MI (CK-MB > 3 times normal) occurred in 14% of patients. Mean reference vessel diameter was 3.28 mm. Mean diameter stenosis was reduced from 63.5% to a final stenosis of 7%. Late 1-year clinical follow-up revealed one cardiac death and a target lesion revascularization rate of 17.8%. The angiographic restenosis rate at 6 months was 28.9%, with the major predictor of restenosis being a smaller postprocedure lumen diameter. CONCLUSIONS: Optimal DCA produced a low residual percent diameter stenosis and a lower restenosis rate than seen in previous trials without an increase in early or late major adverse events.

Directional coronary atherectomy (DCA): a report from the New Approaches to Coronary Intervention (NACI) registry.

Directional coronary atherectomy (DCA) with the Simpson coronary atherocath seeks to debulk rather than simply displace obstructive tissue and is a means of enlarging the stenotic coronary lumen. This report from the New Approaches to Coronary Intervention (NACI) registry describes the experience of 1,196 patients who underwent DCA as the sole treatment for either native vessel or vein graft lesions. Device success (post-DCA residual stenosis <50% and > or =20% improvement) was achieved in 87.8%, with a lesion success rate (postprocedural residual stenosis <50% and > or =20% improvement) of 94.0%. The mean resultant stenosis after all interventions (by core laboratory) was 19%. Significant in-hospital complications occurred in 2.8% of patients with DCA attempts, including death 0.6%, Q-wave myocardial infarction (MI) 1.5%, and emergent coronary artery bypass graft surgery (CABG) 2.8%. At 1-year follow-up, cumulative mortality was 3.6%, with repeat revascularization in 28% (repeat percutaneous transluminal coronary angioplasty, 20.1%; CABG, 10.6%). This reflected percutaneous or surgical revascularization of the original lesion (target lesion revascularization) in 22.6% of patients. Subgroup analysis showed a lower lesion success rate and an increased complication rate for unplanned use, vein graft treatment, and treatment of a de novo (vs a restenotic) lesion. Multivariate analysis shows that diabetes mellitus, unstable angina, treatment of a restenotic lesion, and greater residual stenosis after the initial procedure were independent predictors of the composite endpoint of death/Q-wave MI/target lesion revascularization by 1-year follow-up. Among these generally favorable acute and 1-year results, the NACI directional atherectomy data confirm the "bigger is better" hypothesis: that lesions with a lower residual stenosis after a successful procedure had significantly fewer target lesion revascularizations between 30 days and 1 year, with no increase in major adverse events.

Fatal interstitial pulmonary disease in a patient with dyskeratosis congenita after allogeneic bone marrow transplantation.

Chronic restrictive lung disease in a 9-year-old boy with dyskeratosis congenita (DC) 7 years after allogeneic bone marrow transplantation (BMT) is described. When he was 1 year and 10 months old, severe aplastic anemia developed. He received a marrow transplant from his HLA serologically identical, but HLA-DP mismatched brother. He developed grade II acute graft-versus-host disease (GVHD) and thereafter chronic GVHD of progressive type, and was treated with both prednisolone and azathioprine resulting in clinical improvement. Thereafter he complained of dyspnea, and bilateral noncircumscribed interstitial shadows on chest CT scan were present. His pulmonary function showed restrictive changes. Prednisolone was not effective and he died of respiratory failure. Post-mortem examination confirmed interstitial fibrosis, lymphocytic infiltration of the bronchioles and alveoli with luminal fibrosis. There was no evidence of chronic GVHD in the skin and the liver. These findings raise the possibility that this pulmonary complication was associated with DC itself.

Successful engraftment of allogeneic CD34-enriched marrow cell transplantation from HLA-mismatched parental donors.

The CD34 antigen is expressed on pluripotent stem cells and the CD34+ cell has been shown to be capable of hematopoietic reconstitution in animal and human autologous grafts. We asked if CD34+ cells could reconstitute hematopoiesis in human allogeneic transplantation from a HLA-mismatched donor. Three pediatric patients with advanced leukemia received allogeneic CD34-enriched marrow cell graft from HLA two (two patients) or three (one patient) loci-mismatched parental donors. CD34+ cell selection was performed with mouse anti-CD34 antibody 9C5 and magnetic beads coated sheep anti-mouse IgG1. 1.53 to 2.48 x 10(9) marrow cells were processed and 2.53 to 7.89 x 10(7) positively selected cells were recovered. The selected population showed 93.7 to 99.0% CD34+ cells and total recovery of CD34+ cells from the starting population was 54.6 to 62.3%. CD34+ cell selection resulted in more than 99.9% depletion of CD5+ cells from the bone marrow. The patients received 2.53 to 7.25 x 10(6) CD34-enriched cells/kg after myeloablative therapy. All patients achieved trilineage engraftment that was confirmed by various genetic markers. Acute graft-versus-host disease (GVHD) was grade 0 (two patients) or grade I (one patient), and hematological recovery was successfully achieved as follows; the days to reach granulocytes over 0.5 x 10(9)/I were 11 to 13 days, reticulocytes over 2% was 18 to 28 days, platelets over 50 x 10(9)/I was 33 to 58 days. One patient is surviving without relapse of leukemia and two patients died after either mixed hematopoietic chimerism or leukemia relapse was observed. These studies suggest that CD34+ marrow cells are capable of hematopoietic reconstitution from HLA two or three loci-mismatched donors even with the lowest dose of mature T cells.

Beta ig-h3, a transforming growth factor-beta-inducible gene, is overexpressed in atherosclerotic and restenotic human vascular lesions.

Transforming growth factor-beta (TGF-beta) plays an important role in vascular lesion formation and possibly the renarrowing process ("restenosis") that occurs after balloon angioplasty. Secreted in a latent form by most cells, TFG-beta requires enzymatic conversion before it is biologically active. TGF-beta-inducible gene h3 (beta ig-h3) is a novel molecule that is induced when cells are treated with TGF-beta1. This study examined the expression of beta ig-h3 in normal and diseased human vascular tissue. To determine the expression pattern of beta ig-h3 in human arteries, immunocytochemistry was performed on tissue sections from (1) normal internal mammary arteries, (2) the proximal left anterior descending coronary artery (with minimal intimal thickening) of 15 patients aged 18 to 40 years, (3) primary and restenotic coronary lesions from 7 patients, and (4) fresh directional atherectomy tissue from 11 patients. A polyclonal antibody consistently immunodetected beta ig-h3 protein in endothelial cells of all vascular tissue. In normal coronary arteries of young individuals, beta ig-h3 protein was absent from the intima and media but was found in the subendothelial smooth muscle cells of some arteries with modest intimal thickening. In diseased arteries beta ig-h3 protein was more abundant in the intima than the media. Restenotic coronary lesions tended to show higher levels of immunodetectable beta ig-h3 protein, especially in areas of dense fibrous connective tissue. Beta ig-h3 protein was immunodetected in the cytoplasm of plaque macrophages as well as smooth muscle and endothelial cells. By using in situ hybridization on fresh directional atherectomy specimens, we found beta ig-h3 mRNA to be overexpressed by plaque macrophages and smooth muscle cells. Nondiseased human internal mammary arteries also expressed beta ig-h3 mRNA in endothelial cells but not in the smooth muscle cells of the normal intima and media. These results document the expression of beta ig-h3 in diseased human arterial tissue and support the hypothesis that active TGF-beta plays a role in atherogenesis and restenosis.

I-cell disease: report of an autopsy case.

The history and findings at autopsy of a 9-year-old female with I-cell disease are reported. She manifested gargoyle face, progressive psychomotor retardation, and increased serum levels of lysosomal enzymes with decreased activities in peripheral blood lymphocytes. She received a bone marrow transplantation from her HLA-mismatched father when she was 8 years old. Rejection followed, and 9 months later, she died of cardiac failure secondary to aortic regurgitation. The characteristic inclusion bodies, ultrastructurally corresponding to double-membranous lamellar vacuoles and empty single membrane-bound vacuoles, were identified in dermal fibro blasts, macrophages, glomerular epithelial cells, cardiomyocytes and smooth muscle cells. Pale bodies, faintly eosinophilic cytoplasmic globular inclusions immunoreactive for plasma proteins, were observed in hepatocytes and renal collecting tubular epithelial cells. Enzyme histochemical analyses were performed for N-acetyl-beta-glucosaminidase, beta-glucuronidase, nonspecific esterase and acid phosphatase. Decreased activities of the acid hydrolases and their diffusion in the cytoplasm were seen in Kupffer's cells. Ultrastructural localization of acid phosphatase activity suggested the labilization of the lysosomal membrane. The abnormality in the intracellular transport of the acid hydrolases into the lysosomes in I-cell disease is briefly reviewed and discussed.

Directional atherectomy of coronary and saphenous vein graft ostial stenoses.

Directional coronary atherectomy (DCA) has been proposed as an alternative to balloon dilatation for treating coronary ostial stenoses, but the long-term efficacy of this procedure has not been well studied. To determine the procedural success and long-term efficacy of DCA for ostial stenoses, clinical data from 1 large registry database and from 2 single centers were retrospectively reviewed. Patients included in the study underwent DCA of aortocoronary (left main or right coronary artery), non-aortocoronary (left anterior descending or circumflex), or vein graft ostial stenoses. In 158 patients undergoing DCA of 160 lesions (30 left main or right coronary, 73 left anterior descending or circumflex, and 57 vein graft stenoses), overall procedural success, defined as < 50% residual stenosis without death, Q-wave myocardial infarction, or need for urgent bypass graft surgery, was 87%. The major complication rate was 0.6%. There were no deaths or Q-wave infarctions; only 1 patient required urgent bypass surgery. Other complications included non-Q-wave myocardial infarction (9%), arterial dissection (9%), abrupt closure (4%), and distal coronary embolization (4%). Angiographic follow-up was available for 65% of the 138 eligible patients. The overall 6-month angiographic restenosis rate, defined as > 50% diameter stenosis at the site of DCA, was 48% (de novo lesions 40% and restenotic lesions 61%). Restenosis rates for de novo and restenotic lesions were: aortocoronary (33%/50%), native coronary (38%/35%), and vein graft (47%/93%), respectively. We conclude that DCA of ostial stenoses is an effective revascularization strategy associated with a high procedural success rate and a low incidence of major complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Transition of T cell receptor gamma/delta expressing double negative (CD4-/CD8-) lymphocytes after allogeneic bone marrow transplantation.

We studied peripheral blood CD4-CD8- gamma/delta T cells in recipients of allogeneic marrow grafts, using three-color immunofluorescence and flow cytometry, and investigated changes in their numbers in relation to the administration of hematopoietic growth factors or chronic graft-versus-host disease (GVHD). In the early post-bone marrow transplantation (BMT) period, the relative and absolute numbers of peripheral CD4-CD8- gamma/delta T cells in 22 allogeneic marrow graft recipients in relation to the use of hematopoietic growth factors were studied. During the first 4 weeks, increased numbers of CD4-CD8- gamma/delta T cells were observed in recipients of either recombinant human granulocyte colony-stimulating factor (rhG-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF). However, 4-8 weeks after BMT, the number of these cells was similar in both groups whether or not growth factors had been administered. At a later stage after BMT (3-12 months), peripheral CD4-CD8- gamma/delta T cells from 43 allogeneic BMT recipients were studied. These cells were markedly decreased in patients with chronic GVHD, and this decrease correlated closely with the clinical signs of chronic GVHD. These results suggest that CD4-CD8- gamma/delta T cells may play an important role in the recovery of neutrophils associated with growth factors during the very early post-BMT period, and in the immunodeficient state of chronic GVHD at a later stage after BMT.