Interactions between angiotensin-I converting enzyme insertion/deletion polymorphism and response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin: the lipoprotein and coronary atherosclerosis study.

OBJECTIVES: Our objectives were to determine whether angiotensin-1 converting enzyme (ACE) insertion/deletion (I/D) polymorphism was associated with the severity of coronary artery disease (CAD) and its progression/regression in response to fluvastatin therapy in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) population. BACKGROUND: Genetic factors are involved in susceptibility to CAD. Angiotensin-1 converting enzyme I/D polymorphism, which accounts for half of the variance of plasma and tissue levels of ACE, has been implicated in susceptibility to CAD and myocardial infarction (MI). METHODS: Angiotensin-1 converting enzyme genotypes were determined by polymerase chain reaction (PCR). Fasting plasma lipids were measured and quantitative coronary angiograms were obtained at baseline and 2.5 years following randomization to fluvastatin or placebo. RESULTS: Ninety-one subjects had DD, 198 ID and 75 II genotypes. The mean blood pressure, minimum lumen diameter (MLD), number of coronary lesions and total occlusions were not significantly different at baseline or follow-up among the genotypes. There was a significant genotype-by-treatment interaction for total cholesterol (p = 0.018), low-density lipoprotein cholesterol (LDL-C) (p = 0.005) and apolipoprotein (apo) B (p = 0.045). In response to fluvastatin therapy, subjects with DD, compared with those with ID and II genotypes, had a greater reduction in total cholesterol (19% vs. 15% vs. 13%), LDL-C (31% vs. 25% vs. 21%) and apo B (23% vs. 15% vs. 12%). Definite progression was less (14%) and regression was more common (24%) in DD as compared with those with ID (32% and 17%) and II (33% and 3%) genotypes (p = 0.023). Changes in the mean MLD and lesion-specific MLD also followed the same trend. CONCLUSIONS: Angiotensin-1 converting enzyme I/D polymorphism is associated with the response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin. Subjects with DD genotype had a greater reduction in LDL-C, a higher rate of regression and a lower rate of progression of CAD.

Hemodilution as a method to reduce transfusion requirements in adolescent spine fusion surgery.

STUDY DESIGN: A case-control study. OBJECTIVES: 1) To determine if hemodilution adequately meets the transfusion needs in children who undergo posterior spinal fusion for idiopathic scoliosis and 2) to compare the efficacy of the various methods used to reduce the risk of allogeneic blood transfusion at the authors' institution. SUMMARY OF BACKGROUND DATA: Methods to reduce blood loss and avoid allogeneic blood transfusion caused by extensive spinal surgery in adolescents include 1) autologous blood predonation, 2) controlled hypotensive anesthesia, 3) intraoperative salvage of shed blood (cell saver), 4) acute normovolemic hemodilution, and 5) transfusion decisions by clinical judgment rather than by a preset value of hemoglobin. Although all methods have some efficacy, it is not clear which methods, separate or combined, are best in the adolescent scoliosis population. METHODS: Hemodilution, hypotensive anesthesia, and cell saver were used in 43 children between June 1996 and July 1997. A comparison group (43 children) underwent similar surgery with hypotensive anesthesia and cell saver, but no hemodilution (between July 1995 and December 1996). These two groups were similar with respect to means of age, levels of instrumentation, magnitude of curvature, estimated blood volume, mean arterial pressure, duration of surgery, duration of anesthesia, estimated blood loss, volume returned from cell saver, volume in the hemovac drain, and length of hospitalization. The groups differed in preoperative hemoglobin and hematocrit and in volume of crystalloid used. RESULTS: Transfusions were given to 34 of 43 patients (79%) in the nonhemodilution group. These patients received 61 units of packed cells (57 autologous, 2 donor directed, and 2 allogeneic). In comparison, 16 of 43 patients (37%) in the hemodilution group required transfusion. They received 16 units of packed cells (15 autologous and 1 allogeneic). There was no significant difference between the groups with respect to postoperative hemoglobin and hematocrit immediately after surgery (hemodilution, 10.2/29.2; nonhemodilution, 10.0/29.1), postoperative day 1 (hemodilution, 9.2/26.9; nonhemodilution, 9.2/27.3), and postoperative day 2 (hemodilution 9.0/26.4; nonhemodilution, 9.2/27.1). There were non complications related to the technique of hemodilution in the 43 patients of this group. Cell saver was used in all patients, but sufficient volume to return blood to the patient was available in only 23 hemodilution patients (mean volume, 230 mL) and 25 nonhemodilution patients (mean volume, 215 mL). In only two patients of each group (< 5%) did the volume returned prevent the absolute need for additional transfusions. CONCLUSIONS: Hemodilution was safely used as a method to satisfy the perioperative transfusion requirements of adolescents undergoing extensive spinal surgery. By allowing patients to arrive at surgery with a higher preoperative hemoglobin and hematocrit, and by decreasing the quantity of predonated autologous blood-collected and therefore used, the hemodilution method may indirectly decrease the quantity of postoperative autologous transfusions in this population. Cell saver was not shown to be effective, and its selective use is recommended.

A variant of beta fibrinogen is a genetic risk factor for coronary artery disease and myocardial infarction.

BACKGROUND: Coronary artery disease is a complex trait caused by a number of genetic and environmental factors. Genes involved in hemostasis and coagulation are excellent candidate genes for CAD and its thrombotic complications, i.e., myocardial infarction (MI) and unstable angina. METHODS: We determined the frequency of beta-fibrinogen genotypes in a homogenous patient population with CAD undergoing coronary angioplasty and in a comparable group in the general population. DNA was extracted from the blood and genotypes were determined by polymerase chain reaction, restriction mapping with Hha-1 and gel electrophoresis. Cases and controls were also genotyped for a G17382T polymorphism in the (beta-Myosin heavy chain) (beta-MyHC) gene, which is not a candidate gene for CAD. RESULTS: The distribution of beta-MyHC G/T genotypes and the frequency of alleles were similar in cases and controls. However, the beta-fibrinogen G/G genotype was present in 71% of patients with CAD as compared to 54% in the general population (p = 0.00001, OR: 2.1, 95% CI: 1.7-2.8). Seventy-one percent of patients with MI and 72% of patients with unstable angina had G/G genotype (p = 0.003, OR: 2.0, 95% CI: 1.3-3.3, and p = 0.005, OR: 2.1, 95% CI: 1.3-3.7, respectively). Sixty-nine percent of male and 82% of female patients with CAD had the G/G genotype as compared to 56% and 53% in in general population, respectively (p = 0.0381, and 0.0003, respectively). Multivariate regression analysis showed that the allele G was an independent predictor of case-control status or risk of MI in a codominant manner (F = 86.8 p < 0.0001). CONCLUSIONS: beta-fibrinogen G/G genotype is a genetic risk factor for predisposition to CAD and its thrombotic complications.

Effect of antagonism of mivacurium-induced neuromuscular block on postoperative emesis in children.

The routine use of cholinesterase inhibitors to antagonize residual neuromuscular block may be associated with increased postoperative emesis. Rapid spontaneous recovery from mivacurium may obviate the need for these drugs. In this randomized, double-blind, placebo-controlled study of 113 healthy children who had received mivacurium as part of a standardized anesthetic regimen, we compared the incidence of postoperative complications after spontaneous recovery and after the use of neostigmine-glycopyrrolate or edrophonium-atropine. The anesthetic regimen consisted of halothane, nitrous oxide, fentanyl, 2 micrograms/kg intravenous (i.v.), mivacurium in an initial dose of 0.2 mg/kg, followed by an infusion, adjusted to maintain > or = 1 evoked contraction response to a supramaximum train-of-four stimulus. At the end of the procedure, patients received by random assignment one of three drug combinations: 1) neostigmine 70 micrograms/kg + glycopyrrolate 10 micrograms/kg, i.v., 2) edrophonium 1 mg/kg + atropine 10 micrograms/kg, i.v., and 3) saline. The trachea was extubated when evoked responses to peripheral nerve stimulation and clinical signs of adequate neuromuscular recovery were present. Postoperative pain was treated with morphine and emesis with metoclopramide. There were no significant differences between the three groups with respect to age, surgery, intraoperative fentanyl, and mivacurium use, time from the end of surgery to tracheal extubation, postanesthesia care unit (PACU) arrival and discharge, or in postoperative oxygen saturation values and analgesic requirements. Compared to the placebo group, emesis occurred more often in the PACU in patients receiving the neostigmine-glycopyrrolate combination, but not after edrophonium-atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic instability of myelomeningocele patients during anterior spinal surgery.

Surgery for spinal fusion for patients with myelomeningocele is accompanied by a high rate of complications. The authors report six cases of sudden intra-operative hemodynamic instability which occurred during anterior spinal fusion; the procedures had to be aborted. All children were successfully resuscitated and four patients subsequently underwent successful anterior and posterior spinal fusion. Four of the children had positive skin and serum allergy tests to latex.