Acute occlusion in multiple lesion coronary angioplasty: frequency and management

Among 3,548 patients undergoing a percutaneous transluminal coronary angioplasty procedure, 714 had multilesion angioplasty (1,550 lesions) in a single session. Acute occlusion occurred in 22 patients (3.1%) and 29 lesions (1.9%). The patients were classified into a group undergoing multivessel angioplasty (348 patients, 785 lesions) and a group undergoing multilesion single vessel angioplasty (366 patients, 765 lesions). The rate of acute occlusion was similar in both patient groups. The multivessel angioplasty group had a 2.9% rate per patient (n = 10) and a 1.7% rate per vessel; the multilesion single vessel group had a 3.3% rate per patient (n = 12) and a 2.1% rate per lesion. Five of the 10 patients from the multivessel group with acute occlusion, but only 1 of the 12 patients with occlusion in the single vessel multilesion group, required emergency open heart surgery. No patient in either group died as a consequence of coronary angioplasty. Occlusion occurred during angioplasty in 15 of the 22 patients, and 1 to 24 h after angioplasty in 7 of 22 patients. In the group with multivessel angioplasty, acute occlusion during the procedure was mainly linked with hypotension during the second vessel dilation, whereas in this group with delayed vessel closure and in the multilesion single vessel group, existence of intimal tearing constituted the most important factor for acute occlusion (12 of 16 patients). Closure of vessel per major coronary system was evenly distributed in the multivessel group, whereas significantly more left circumflex vessels closed in the single vessel multilesion group (6.1% versus 1.3% in the left anterior descending coronary artery and 1.1% in the right coronary artery; p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of human recombinant Endostatin protein on human angiogenesis

Tumor growth and metastasis are dependent on the development of new blood vessels. Inhibitors of new vessel growth have been widely investigated as anti-tumor agents. Endostatin, a 20 kDa C-terminal fragment of collagen XVIII inhibits endothelial cell proliferation, induces endothelial cell apoptosis, and can both inhibit and reverse tumor growth in mice. However, human recombinant endostatin has had limited testing against human tissue targets. To investigate the effect of human endostatin on a human vessel target over a broad range of concentrations (10^–12–10^–4 M), human placental vein disks were grown for a period of 2 weeks in a 0.3% fibrin clot overlayed with growth medium. Disks from five individual placentas were tested. For each placenta utilized, a control (medium and 20% fetal bovine serum [FBS]) group and a group treated with heparin (300 g/ml) and hydrocortisone 21-phosphate (350 g/ml) (heparin-steroid) at a dose known to inhibit angiogenesis were included. Endostatin was tested at concentrations of 10^–12–10^–4 M in medium containing 20% FBS. The rate of initiation and the angiogenic growth index (on a visually graded semi-quantitative scale of 0–16) were determined for all experimental conditions. Endostatin inhibited angiogenesis in our model only in high concentrations. At 10^–5 M, endostatin did not alter the percent of wells that initiated an angiogenic response, but significantly inhibited subsequent vessel growth. At 10^–4 M, endostatin was able to inhibit both initiation and subsequent new vessel growth. Human endostatin can inhibit the initiation of a human angiogenic response and inhibit the subsequent proliferation of human neovessels when used at high doses in a continuous exposure model.     

Human Leukocyte Antigens and Cellular Immune Responses to Anthrax Vaccine Adsorbed

Interindividual variations in vaccine-induced immune responses are in part due to host genetic polymorphisms in the human leukocyte antigen (HLA) and other gene families. This study examined associations between HLA genotypes, haplotypes, and homozygosity and protective antigen (PA)-specific cellular immune responses in healthy subjects following immunization with Anthrax Vaccine Adsorbed (AVA). While limited associations were observed between individual HLA alleles or haplotypes and variable lymphocyte proliferative (LP) responses to AVA, analyses of homozygosity supported the hypothesis of a “heterozygote advantage.” Individuals who were homozygous for any HLA locus demonstrated significantly lower PA-specific LP than subjects who were heterozygous at all eight loci (median stimulation indices [SI], 1.84 versus 2.95, P = 0.009). Similarly, we found that class I (HLA-A) and class II (HLA-DQA1 and HLA-DQB1) homozygosity was significantly associated with an overall decrease in LP compared with heterozygosity at those three loci. Specifically, individuals who were homozygous at these loci had significantly lower PA-specific LP than subjects heterozygous for HLA-A (median SI, 1.48 versus 2.13, P = 0.005), HLA-DQA1 (median SI, 1.75 versus 2.11, P = 0.007), and HLA-DQB1 (median SI, 1.48 versus 2.13, P = 0.002) loci, respectively. Finally, homozygosity at an increasing number (≥4) of HLA loci was significantly correlated with a reduction in LP response (P < 0.001) in a dose-dependent manner. Additional studies are needed to reproduce these findings and determine whether HLA-heterozygous individuals generate stronger cellular immune response to other virulence factors (Bacillus anthracis LF and EF) than HLA-homozygous subjects.     

Multiple paths to loss of anergy and gain of autoimmunity

B cells and autoimmunity: cells of the immune system have the capacity to recognize/neutralize a myriad array of disease-causing pathogens, while simultaneously minimizing damage to self tissue. Obvious breakdowns in this ability to distinguish between self and non-self are evident in multiple forms of autoimmune disease, where B and T cells mount damaging attacks on cells and organs. B cells may directly damage tissue by producing pathogenic antibodies that bind self antigen, fix complement or form immune complexes. Recent evidence also suggests B cells indirectly induce autoimmunity by concentrating low avidity self antigen through the B cell receptor and presenting self-peptides to autoreactive T cells. B cells may also initiate autoimmunity when provided sufficient help from autoreactive T cells that have escaped deletion in the thymus. Here, we will review the role of anergy in maintenance of tolerance and how alterations in the normal balance of positive and negative signals may contribute to the development of autoimmune disease in mouse models and humans.