用Sauvegrain法测定青春期骨龄准确性的研究

背景：Sauvegrain方法是通过分析肘部X线片来评估骨龄，常用于青春期生长发育最为迅速的两年间的骨龄测定。本文旨在研究该方法的准确性以及在小儿骨科中的应用价值。 方法：Sauvegrmn法主要评估肘部的4个解剖标志点：外髁、肱骨滑车、尺骨鹰嘴突以及桡骨近端骨骺。它是一个27分制的评分系统。对上述结构所得的评分进行合计而得出一个总分，然后使用标准图表确定骨龄。让三位观察者分别利用该方法进行骨龄评估。三位观察者通过分析60个男孩和60个女孩样本左肘部的前后位和侧位X线片来测定骨龄，并将该结果与通过分析左手和腕部后前位X线片的Greulich和Pyle图谱而得出的骨龄结果进行比较。间隔4周后每个观察者再测定骨龄一次。 结果：通过分析肘部X线片的方法测定骨龄更为精确，因为采用该方法测定骨龄可以精确到半岁。根据观察者的评定，Sauvegrain法显示出很好的观察者之间的相关性（r=0．93）和可重复性（r=0．96）。Sauvegrain法与Greulich和Pyle图谱之间有很好的相关性（r=0．85）。然而，一些肘部生长中心显示出一种中间的发育形态，这种形态学不适合Sauvegrain法的评分。这就导致了数据分析时出现误差。我们建议对于这些样本设定中间评分，并且通过修改原始图表而使评分更为精确。 结论：改良的Sauvegrain法简单、可靠而且可重复性高，它补充了Greulich和Pyle图谱的不足。在临床实践中，骨骼成熟度可以通过骨龄、年生长率以及第二性征而得以很准确的评估。因此，当青春期需要进行骨骺或脊柱关节融合术时，这种方法对于确定手术时间具有重要意义。 可信水平：诊断性研究，Ⅱ级，进一步可信度参见作者介绍。     

Enzymatic methyl esterification of a deamidated form of mouse epidermal growth factor

The enzyme S-adenosylmethionine:protein carboxyl-O-methyl-transferase, type II (EC2.1.1.77; PCMT) from eukaryotes methyl esterifies peptides containing isoAsp residues, which can arise from spontaneous deamidation of labile Asn residues. We report here a study on in vitro methyl esterification of mouse EGF by bovine brain PCMT. This peptide contains two Asn in the sequences Asn¹-Ser² and Asn¹⁶-Gly¹⁷. It is known from the literature that the presence of a small residue on the carboxyl side of asparaginyl makes this residue susceptible to deamidation through the spontaneous formation of a succinimide intermediate. Therefore EGF was incubated under deamidating conditions (pH9.0, 37° for 48 h) and the extent of deamidation monitored by enzymatically measuring the NH₃ produced during the alkali treatment: a release of 0.80 mol NH₃/mol EGF was calculated. The alkali-treated EGF, analyzed by anion-exchange chromatography, shows two major components identified as native EGF (nEGF) and its deamidated form (dEGF). When incubated in the presence of purified PCMT neither nEGF nor dEGF showed any methyl accepting capability. Since it is known that the three-dimensional structure of a protein may hinder the methyl esterification of a potential ethyl accepting site, dEGF was unfolded by reducing and alkylating the intrachain disulfide bridges. Only a slight increase in the methyl accepting capability could be observed. Conversely, when EGF was deamidated after its unfolding, the resulting protein was stoichiometrically methylated by PCMT, presumably at level of isoAsp¹⁶. Our findings strongly suggest that the three-dimensional structure of a protein is a major specificity determinant for both deamidation and methyl esterification processes.     

Conformational preferences and self-association modes of two diastereomeric statine derivatives

The conformational preferences and self-association modes of the two diastereomeric N-acetyl, methylamides of 3-hydroxy, 4-amino, 6-methylheptanoic acid (statine) with (R, S) and (S, S) configurations at the 3-hydroxy and 4-amino carbons, respectively, have been determined in solution as well as in the solid state by infrared absorption, ¹H nuclear magnetic resonance, and X-ray diffraction. Conformational energy computations have also been performed in parallel. In the crystal state, the change in chirality of the hydroxyl group induces different intermolecular H-bonding schemes in the (R, S) isomer compared to the two structurally distinct molecules in the asymmetric unit of the (S, S) isomer. Different propensities to self-aggregate are seen in solvents of low polarity. In solvents of high polarity, however, the molecules of both isomers are largely solvated, while still keeping some local conformational restriction. Conformational energy computations indicate that in vacuo the two diastereomers exhibit different flexibility, and a preferred conformation with a different type of intramolecular H-bond.     

Koch's Triangle in Pediatric Age: Correlation with Extra- and Intracardiac Parameters

The atrioventricular node is situated in the lower atrial septum, at the apex of the Koch's triangle. The dimensions of the Koch's triangle are studied in adult humans, while no data exist about tbem in pediatric age. the knowledge of the dimensions of Koch's triangle in childhood is very important for safe and correct application of radiofrequency energy during transcatheter ablation. The dimensions of Koch's triangle were determined in 69 human pediatric hearts. the median age of the children was 3 months. with a range from 1 day to 14 years, 30 were female and 39 were male. Relations between body weight (extracardiac parameter) and tricuspid valve diameter (intracardiac parameter) were determined in all hearts to sbow morpbometric modifications with growth. the distribution of body weight was not Gaussian and no correlation could be obtained between Koch's triangle dimensions and body weight. However, it was possible to identify that the mean ratio between the cathetus of the Koch's triangle corresponding to the annulus of the tricuspid valve and the tricuspid valve diameter was 0.45 ± 0.16, with a highly significant correlation coefficient (r = 0.653, P < 0.001). Therefore, by knowing: (1) the diameter of the tricuspid valve, and (2) the constant ratio between the cathetus of the Koch's triangle and the tricuspid valve diameter, it is possible to calculate the lengtb of the segment of the tricuspid annulus along wbich the transcatheter application of radiofrequency current can be applied to ablate the slow-pathway, tbus reducing the risks of damage of the atrioventricular node.     

Do European GSM Mobile Cellular Phones Pose a Potential Risk to Pacemaker Patients?

BARBARO, V., et al .: Do European GSM Mobile Cellular Phones Pose a Potential Risk to Pacemaker Patients? A series of in vivo trials were carried out in order to verify whether the electromagnetic field radiated by GSM (Groupe Systemes Mobiles) mobile cellular phones might affect implanted pacemakers. Two European GSM phones of 2-watt power were tested and trials conducted on 101 pacemaker implanted outpatients attending day hospital for routine check-up, who volunteered for trials. Forty-three pacemaker models from 11 manufacturers were tested in all. When the sensing threshold of the pacemakers was set at a minimum and the antenna of the phone was in direct contact with the patient's chest, interference was detected for 26 implanted pacemakers. Specifically, pulse inhibition in 10 of 101 cases, ventricular triggering in 9 of 46 DDD-VDD pacemakers, and asynchronous pacing in 4 of 52 devices. Pulse inhibition was also observed combined with asynchronous pacing in 1 of 52 cases and with ventricular triggering in 2 of 46 cases. Minimum effect duration was ca. 3 seconds but in 6 cases effects continued as long as the interfering GSM signal was on. No permanent malfunctioning or changes in the programmed parameters were detected. Whenever interference was detected, trials were repeated to determine the maximum sensing threshold at which interference persisted (with the antenna in contact with the skin over the pacemaker). Then maximum distance between antenna and pacemaker at which interference occurred was determined at pacemaker maximum and minimum sensing threshold. Under our experimental conditions electromagnetic interference effects were detected at a maximum distance of 10 cm with the pacemaker programmed at its minimum sensing threshold. When the phone antenna was in direct contact with patient's skin over the implant, electromagnetic interference effects occurred at maximum ventricular and atrial sensing thresholds of 4 mV and 2.5 mV, respectively.     

Electromagnetic Interference of Analog Cellular Telephones with Pacemakers

The aim of this study was to verify whether there is a public health risk from the interference of analog cellular telephones with pacemakers. We used a human trunk simulator to reproduce an actual implant, and two cellular telephones working with the TACS (Total Access Communication System) standard. Results showed that the electromagnetic field radiated from the analog cellular telephones interfered with a large number of the pacemakers tested (10/25). When the telephone antenna was in close proximity to the pacemaker head, pacemaker desensitizing and sensitizing and pulse inhibition was detected at the moment of an incoming call and throughout ringing. In the worst case of pulse inhibition, the pacemaker skipped three nonconsecutive beats and then resumed its normal pacing, while the desensitizing and sensitizing phenomena persisted as long as the interfering signal was on. Pulse inhibition was also observed when the connection did not succeed. Maximum sensing threshold variation was about 186% (increase) and 62% (decrease) for desensitizing and sensitizing phenomena, respectively. It was also demonstrated that the signal emitted by analog cellular telephones during the crossing of contiguous cells could induce pacemaker pulse inhibition, but under our experimental conditions this event did not seem to pose a risk for the pacemaker patient.     

Long-Term Results of Hybrid Therapy in Patients with Atrial Fibrillation Who Develop Atrial Flutter During Flecainide Infusion

The flecainide infusion test has been proposed to screen candidates for hybrid pharmacological and ablation therapy. We report the long-term follow-up of 154 consecutive patients with paroxysmal or persistent atrial fibrillation (AF) who developed atrial flutter (AFL) during flecainide infusion (IC AFL), treated with inferior vena cava-tricuspid annulus isthmus catheter ablation and oral flecainide (hybrid therapy). Over a mean of 54.1 ± 13.1 months 82 patients (53%) remained free of AF and AFL. Flecainide was discontinued because of adverse effects in 6 patients (4%). A history of persistent AF, and the documentation of ≥1 spontaneous AFL episode before the flecainide test were independent predictors of successful hybrid therapy. In patients with paroxysmal AF without documented spontaneous AFL, the long-term efficacy of hybrid therapy was 38.5% (P = 0.03). The flecainide infusion test reliably detects candidates for hybrid therapy. The efficacy of this therapy is maintained over the long-term with a high patient compliance.     

Molecular Biology of the Long QT Syndrome: Impact on Management

The long QT syndrome (LQTS) is a familial disease characterized by prolonged ventricular repolarization and high incidence of malignant ventricular tachyarrhythmias often occurring in conditions ofadrenergic activation. Recently, the genes for the LQTS linked to chromosomes 3 (LQT3), 7 (LQT2), and 11 (LQTl) were identified as SCN5A, the cardiac sodium channel gene and as HERG and KvLQTl potassium channel genes. These discoveries have paved the way for the development of gene-specific therapy for these three forms of LQTS. In order to test specific interventions potentially beneficial in the molecular variants of LQTS, we developed a cellular model to mimic the electrophysiological abnormalities of LQT3 and LQT2. Isolated guinea pig ventricular myocytes were exposed to anthopleurin and dofetilide in order to mimic LQT3 and LQT2, respectively. This model has been used to study the effect of sodium channel blockade and of rapid pacing showing a pronounced action potential shortening in response to Na⁺channel blockade with mexiletine and during rapid pacing only in anthopleurin-treated cells but not in dofetilide-treated cells. Based on these results we tested the hypothesis that QT interval would shorten more in LQT3 patients in response to mexiletine and to increases in heart rate. Mexiletine shortened significantly the QT interval among LQT3 patients but not among LQT2 patients. LQT3 patients shortened their QT interval in response to increases in heart rate much more than LQT2 patients and healthy controls. These findings suggest thatLQT3 patients are more likely to benefit from Na⁺ channel blockers and from cardiac pacing because they are at higher arrhythmic risk at slow heart rates. Conversely, LQT2 patients are at higher risk to develop syncope under stressful conditions, because of the combined arrhythmogenic effect of cate-cholamines with the insufficient adaptation of their QT interval. Along the same line of development of gene-specific therapy, recent data demonstrated that an increase in the extracellular concentration of potassium shortens the QT interval in LQT2 patients suggesting that intervention aimed at increasing potassium plasma levels may represent a specific treatment for LQT2. The molecular findings on LQTS suggest the possibility of developing therapeutic interventions targeted to specific genetic defects. Until definitive data become available, antiadrenergic therapy remains the mainstay in the management of LQTS patients, however it may be soon worth considering the addition of a Na + channel blocker such as mexiletine for LQT3 patients and of interventions such as K⁺ channel openers or increases in the extracellular concentration of potassium for LQTl and LQT2 patients.