Importance of delaying balloon angioplasty in patients with unstable angina pectoris

Angioplasty in patients with unstable coronary artery disease is associated with higher complication rates compared with patients with stable disease. In this report we describe our results from a group of patients with unstable disease (unstable angina pectoris and postmyocardial infarction) where a strategy of delaying angioplasty for >5 days after admission was undertaken. Included are 2069 consecutive patients: 1197 treated for stable angina pectoris and 872 treated during admission for unstable angina or myocardial infarction. There was no difference between the two groups in angioplasty success (92.1% stable, 92.3% unstable), failure to dilate without complication (6.4% stable, 6.1 % unstable), or in the rate of major complications: death (0.5% stable, 1.1% unstable), Q-wave myocardial infarction (0.9% stable, 1.1% unstable), and emergency coronary artery bypass (0.6% stable, 0.3% unstable). The duration of hospitalization following angioplasty was longer in the unstable group (5.6 ± 8.1 days vs. 4.2 ± 4.1 days; p < 0.001) because of longer duration of hep-arin infusion. There was no difference between groups in minor complications such as groin hematoma and pseudoa-neurysm, renal failure, or infections. It was concluded that delaying angioplasty in unstable patients for > 5 days after admission is a safe and effective therapeutic strategy for this group of patients. The need for prolonged heparin infusion after angioplasty is increased in unstable patients and thus the duration of hospitalization after the procedure is longer.     

Treating Acute “No-Reflow” with Intracoronary Adenosine in 4 Patients during Percutaneous Coronary Intervention

Angiographic evidence of impaired tissue perfusion, known as the “no-reflow” phenomenon, is a serious complication of percutaneous coronary intervention—one that is associated with increased mortality rates. Adenosine is an endogenous nucleoside that attenuates many of the mechanisms that are responsible for no-reflow. Herein, we report the cases of 4 patients who developed the no-reflow phenomenon after elective percutaneous coronary intervention to their native coronary arteries and saphenous vein grafts. In all 4 patients, and without adverse effects, small bolus doses of adenosine through the guiding catheter improved epicardial perfusion—measured by either Thrombolysis In Myocardial Infarction (TIMI) flow grade or corrected TIMI frame count—and tissue-level perfusion, graded according to myocardial blush. In view of adenosine''s extremely short half-life in blood, the continuous administration of adenosine into the distal vascular bed throughout percutaneous coronary intervention may further improve outcomes by reversing or preventing the no-reflow phenomenon.Key words: Adenosine/administration & dosage/physiology/therapeutic use, angioplasty, transluminal, percutaneous coronary/adverse effects/methods, atherosclerosis/complications/therapy, cardiotonic agents/administration & dosage/therapeutic use, coronary vessels/drug effects, creatine kinase/blood, dose-response relationship, drug, graft occlusion, vascular/therapy, myocardial reperfusion/methods, treatment outcome, vasodilator agents/administration & dosage/therapeutic usePercutaneous coronary intervention (PCI) is frequently used to treat atherosclerosis-induced stenosis in native coronary arteries and in degenerated saphenous vein grafts (SVGs). Although PCI has a high initial success rate, enzymatic evidence of myocardial cell necrosis occurs in 22% to 44% of patients after apparently uneventful PCI procedures.^1,2 Microvascular obstruction (due in part to embolization of platelets and atheromatous débris) and intense vasoconstriction of the distal bed (secondary to the release of potent humoral mediators) are responsible for microinfarction after PCI.^3–6 In some patients, vascular compromise manifests itself during the procedure as an abrupt decrease in epicardial blood flow—Thrombolysis In Myocardial Infarction (TIMI) grade 0 to 1—which is known as the “no-reflow” or “slow-reflow” phenomenon. The compromise occurs in the absence of apparent dissection, coronary spasm, thrombus formation, substantial residual stenosis, or distal-vessel cutoff that is suggestive of macroembolization.Adenosine attenuates mechanisms that are responsible for the no-reflow phenomenon.⁷ We describe here the cases of 4 patients in whom intracoronary adenosine reversed no-reflow during PCI of the native coronary vessels and SVGs, as measured by TIMI flow grade, corrected TIMI frame count (CTFC), and myocardial blush grade (MBG).     

Autosomal-dominant nystagmus,foveal hypoplasia and presenile cataract associated with a novel PAX6 mutation

Autosomal-dominant idiopathic infantile nystagmus has been linked to 6p12 (OMIM 164100), 7p11.2 (OMIM 608345) and 13q31-q33 (OMIM 193003). PAX6 (11p13, OMIM 607108) mutations can also cause autosomal-dominant nystagmus, typically in association with aniridia or iris hypoplasia. We studied a large multigenerational white British family with autosomal-dominant nystagmus, normal irides and presenile cataracts. An SNP-based genome-wide analysis revealed a linkage to a 13.4-MB region on chromosome 11p13 with a maximum lod score of 2.93. A mutation analysis of the entire coding region and splice junctions of the PAX6 gene revealed a novel heterozygous missense mutation (c.227C>G) that segregated with the phenotype and is predicted to result in the amino-acid substitution of proline by arginine at codon 76 p.(P76R). The amino-acid variation p.(P76R) within the paired box domain is likely to destabilise the protein due to steric hindrance as a result of the introduction of a polar and larger amino acid. Eye movement recordings showed a significant intrafamilial variability of horizontal, vertical and torsional nystagmus. High-resolution in vivo imaging of the retina using optical coherence tomography (OCT) revealed features of foveal hypoplasia, including rudimentary foveal pit, incursion of inner retinal layers, short photoreceptor outer segments and optic nerve hypoplasia. Thus, this study presents a family that segregates a PAX6 mutation with nystagmus and foveal hypoplasia in the absence of iris abnormalities. Moreover, it is the first study showing detailed characteristics using eye movement recordings of autosomal-dominant nystagmus in a multigenerational family with a novel PAX6 mutation.     

False-positive results in ELISA-based anti FVIII antibody assay may occur with lupus anticoagulant and phospholipid antibodies

Summary. The evaluation of a prolonged aPTT often includes Lupus Anticoagulant, Antiphospholipid Antibodies, and Factor VIII (FVIII) inhibitors. We have noticed that patient samples positive for lupus antibody (LA) are frequently also positive for FVIII IgG antibodies in an enzyme‐linked immunosorbent assay (ELISA), indicating the need for follow‐up testing with a more labour‐intensive functional assay for FVIII inhibition. This study evaluates the potential for a FVIII IgG ELISA to yield false‐positive results in patient samples positive for LA or other antiphospholipid antibodies. A total of 289 residual de‐identified patient samples positive for LA (n = 143), anti‐cardiolipin IgG (n = 84), or beta2‐glycoprotein antibody (n = 62) were tested for FVIII IgG using a commercial ELISA. Samples with positive FVIII IgG ELISA results were further tested for FVIII activity using a clot‐based FVIII inhibitor assay. The FVIII IgG ELISA yielded positive results in 39 (13%) of the samples tested, including 13/143 (13%) LA‐positive, 15/85 (18%) aCL IgG‐positive and 6/62 (10%) β2‐glycoprotein IgG‐positive samples. The clot‐based FVIII inhibitor assay yielded negative results in all 39 FVIII IgG‐positive specimens tested, indicating discrepancy with the FVIII IgG ELISA results. Patient specimens positive for LA, aCL IgG, or β2‐glycoprotein IgG may yield false‐positive results for FVIII antibodies. Caution is warranted in interpreting FVIII antibody results in these cases.     

Teratogenesis in repeated pregnancies in antiepileptic drug‐treated women

Purpose: Considerable information is now available concerning the risk of teratogenesis in the individual pregnancy exposed to antiepileptic drugs (AEDs). However, there is comparatively little information available concerning the risk in the subsequent pregnancies of women who continue to take the AED associated with a fetal malformation in a previous pregnancy. This article addresses this matter. Methods: Analysis of data concerning fetal abnormalities in 1,243 women who had 2,637 pregnancies between mid‐1999 and 2010 recorded in the Australian Register of Antiepileptic Drugs in Pregnancy. Of the 2,637 pregnancies, 1,114 had been completed before initial enrolment in the Register. Key Findings: Women taking any AED who had given birth to a malformed baby in their first enrolled pregnancy and who continue taking the same drug were at increased risk of having a malformed offspring in their next pregnancy (35.7% vs. 3.1%; odds ratio [OR] 17.6; 95% confidence interval [95% CI] 4.5–68.7). Among these women, those taking valproate (VPA) were more likely to have malformed fetuses in their next pregnancies than those who had taken VPA without fetal abnormalities (57.2% vs. 7.0%, OR 17.8; 95% CI 2.7, 119.1). There were similar although not statistically significant trends in those who had taken AEDs other than VPA. Similar, although again not statistically significant, trends were found, when considering the pairings of the most recent preenrollment pregnancy and the following one. If a woman had two or more pregnancies that resulted in AED‐associated fetal malformation, the types of malformation were often different. Significance: Women whose last pregnancy resulted in a fetal malformation have a substantially increased risk of having further malformed fetuses if they become pregnant again while taking the same AED, particularly VPA. This suggests that maternal factors, perhaps genomic, predispose to at least VPA‐associated malformations. This knowledge, together with information about the outcome of any previous pregnancy, should help in advising women with AED‐treated epilepsy who plan further pregnancies.