Oral Loading with Propafenone: A Placebo-Controlled Study in Elderly and Nonelderly Patients with Recent Onset Atrial Fibrillation

The efficacy and safety of propafenone as an oral loading dose (600-mg single oral dose) in converting recent-onset atrial fibrillation (≤ 7 days duration) to sinus rhythm were evaluated in a single-blind, placebo-controlled study according to patients' age. Overall, 240 hospitalized patients, NYHA Class ≤ 2 without signs or symptoms of heart failure were enrolled: among patients aged ≤ 60 years, 55 were allocated to propafenone treatment and 59 to placebo, respectively, and among patients aged > 60 years, 64 were allocated to propafenone treatment and 62 to placebo, respectively. Results: In each age group, the likelihood of conversion to sinus rhythm was significantly greater after propafenone compared with plocebo at 3 and 8 hours. For patients aged ≤ 60 years, corresponding odd ratios were 3.78 (95% CI = 1.80–7.92, P = 0.04) at 3 hours and 4.74 (95% CI = 2.12–10.54, P = 0.02) at 8 hours; for patients aged > 60 years odd ratios were 5.03 (95% CI = 2.08–12.12, P = 0.02) at 3 hours and 6.75 (95% CI = 3.28–73.86, P = 0.01) at 8 hours, respectively. Logistic regression analysis showed that conversion to sinus rhythm within 3 hours was predicted by age ≤ 60 years (P = 0.0064) and by propafenone treatment (P < 0.0001), and conversion to sinus rhythm within 8 hours was predicted by age ≤ 60 years (P = 0.0467) and by propafenone treatment (P < 0.0001). The occurrence of adverse effects was observed in 14%-16% of propafenone treated patients and in 8% of placebo treated patients without significant differences according to age. In conclusion, in patients with recent-onset atrial fibrillation without signs of heart failure, propafenone as a single oral loading dose is effective. It is also effective in selected elderly subjects with a favorable safety profile. Moreover, spontaneous conversion to sinus rhythm appears to occur less frequently in elderly patients.     

阳春砂1-去氧-D-木酮糖-5-磷酸还原异构酶基因的克隆及表达分析

【目的】克隆阳春砂萜类生物合成途径的上游关键酶——1-去氧-D-木酮糖-5-磷酸还原异构酶(1-deoxy-D-xylulose-5-phosphate reducto iso merase,DXR)(EC:1.1.1.267)的编码基因;分析基因的功能及其在阳春砂不同组织中的表达。【方法】通过基于逆转录—聚合酶链反应(RT-PCR)的方法从阳春砂叶片中获得编码DXR的cDNA全长序列,克隆基因编码区;用生物信息学的方法对其编码蛋白进行相似性检索和功能分析;用半定量RT-PCR法比较基因在阳春砂不同组织中的表达差异。【结果】获得了全长1749bp的编码阳春砂DXR的cDNA序列,命名为AvDXR1(GenBank登记号:FJ459894)。AvDXR1编码的蛋白与其他植物来源的DXR有很高相似性,含有烟酰胺腺嘌呤二核苷酸磷酸(NADPH)结合基序和DXR活性位点基序,N-端有叶绿体靶向转运肽。保守功能结构域的分析结果表明AvDXR1属于1-去氧-D-木酮糖-5-磷酸还原酶家族。AvDXR1在包括茎、根、果皮和种子团的广泛组织中表达,且在这些组织中的表达量均高于在叶片中的表达。【结论】AvDXR1基因是阳春砂DXR的编码基因,该基因在阳春砂的叶、茎、根、果皮和种子团中广泛表达。     

INTERLEUKIN 6 GENE-TRANSFECTED MOUSE MAMMARY ADENOCARCINOMA: TUMOUR CELL GROWTH AND METASTATIC POTENTIAL

Cells from the spontaneous metastatic TSA mammary adenocarcinoma of BALB/C mouse were transfected with the murine (interleukin-6) IL6 gene. The clone (TSA-IL6) secreting the largest amount of IL6 displayed an in vitro increased growth rate compared with that of TSA cells transfected with the neomycin resistance gene only (TSA-neo). TSA-IL6 cell colonies consisted mainly of fusiform cells and TSA-neo colonies of polygonal cells. When subcutaneously (s.c.) injected in syngeneic mice, TSA-IL6 cells gave rise to tumours that grew significantly slower than TSA-neo cell tumours. Microscopically, TSA-IL6 tumours displayed a fascicular pattern of growth, associated with a very scanty macrophage infiltrate. S.c. TSA-IL6 tumours were significantly less metastatic than TSA-neo tumours. By contrast, following intravenous (i.v.) challenge, TSA-IL6 cells produced 5–7 times more lung metastases than TSA-neo cells. The i.v. TSA-IL6 cell lung metastases showed a marked macrophage infiltrate and a rich vascularization. The high in vitro TSA-IL6 cell growth rate is attributable to the IL6-induced production of growth factors, some of which possess heparin-binding properties, such as amphiregulin. The differences in vascularization and macrophage infiltrate may underlie the observed differences between s.c. TSA-IL6 tumour growth with low spontaneous metastatic potential and the widespread growth of i.v. metastasis. © 1997 John Wiley & Sons, Ltd.     

CELLULAR KINETIC AND PHENOTYPIC HETEROGENEITY IN AND AMONG BURKITT'S AND BURKITT-LIKE LYMPHOMAS

This study asks whether the known genotypic heterogeneity within and between endemic or sporadic Burkitt's lymphomas (eBLs and sBLs, n=10 each), and Burkitt-like lymphomas (BLLs, n-12), is reflected in divergent cytokinetics and related immunophenotypes. There was strong evidence that eBL and BLL grow markedly faster than sBL, as shown by differences in mitotic and apoptotic indices. Furthermore, in BLL, the median percentage of neoplastic cells immunoreactive for the bcl-2 protein was much higher than that observed in eBL and sBL. The reverse was true for the median fraction of cells containing c-myc protein. In eBL and sBL, the median fraction of bcl-6 protein-positive cells reached values above 50 per cent, while cells of 8/12 BLLs did not contain detectable amounts of this protein. This observation indicates that in this respect, eBL and sBL resemble normal germinal centres of lymphatic tissue much more than do BLL. Evidence for infection of neoplastic cells by the Epstein-Barr virus (EBV) was observed in 9/10 cases of eBL and in 3/10 of sBL, but not in BLL. EBV-positive lymphomas were associated with distinctly lower apoptotic indices and smaller median percentages of bcl-6-positive cells than EBV-negative tumours. © 1997 John Wiley & Sons, Ltd.     

Continuous epidural block for pain control in bladder exstrophy: report of a case and description of technique

We describe in a neonate an unusual epidural technique for pain control after the surgical correction of bladder exstrophy.     

Achromobacter xylosoxidans respiratory tract infections in cystic fibrosis patients

Achromobacter xylosoxidans is a ubiquitous Gram‐negative non‐fermenting rod, recently characterized as an emerging pathogen in cystic fibrosis (CF) patients. Its pathogenic potential and prevalent transmission routes are still unclear. This study investigated the PFGE genetic pattern and antimicrobial resistance profile of 42 A. xylosoxidans isolates obtained over 4 years from the respiratory tract of 22 CF patients. By genotypic analysis, 31 isolates were attributed to 8 distinct PFGE patterns (A–H), whereas 11 isolates were not typable because their DNA was not restricted by XbaI and DraI restriction enzymes. The majority of the isolates showed multidrug resistance; imipenem and piperacillin were the most active drugs. During the course of A. xylosoxidans chronic infection forced expiratory volume and body mass index values were not significantly lowered. The demonstration of widespread antibiotic resistance underscores the importance of antibiogram‐directed therapy. Our data suggest that in some cases the infection may have been acquired from other patients or from a common contaminated source. Further epidemiological studies may be important for the design and implementation of prophylactic measures in CF centers.     

Conversion of Recent-Onset Atrial Fibrillation to Sinus Rhythm: Effects of Different Drug Protocols

In a population of 417 hospitalized patients, the efficacy and safety of different drug regimens administered to convert atrial fibrillation (AF) of recent anset (≤ 7 days duration) to sinus rhythm were evaluated. All patients were in NYHA Class ≤ 2, and free of heart failure. They were randomly allocated to treatment with placebo in 121 patients; IV amiodarone, 5 mg/kg bolus, followed by 1.8 g/24 hours in 51 patients; IV propafenone, 2 mg/kg bolus, followed by 0.0078 mg/kg/min in 57 patients; p.o. propafenone, 600 mg p.o. in a single dose in 119 patients; and p.o. flecainide, 300 mg p.o. in a single dose in 69 patients. All patients were continuously monitored by Holter ECG, and the number of conversions to sinus rhythm was measured at 1, 3, and 8 hours. Results: (1) IV propafenone resulted in a higher conversion rate within 1 hour compared with the oral loading regimens of propafenone or flecainide, but the conversion rates at 3 and 8 hours were comparable, approximately 75% at 8 hours; 2) IV amiodarone was not different from placebo until 8 hours when it was associated with 57% of conversions; (3) conversion to sinus rhythm at 8 hours was observed in 37% of the placebo treated patients. Serious adverse effects occurred in few patients: two patients treated with flecainide and one treated with IV propafenone experienced left ventricular decompensation; one patient treated with placebo and two treated with flecainide had atrial flutter with rapid ventricular response. In conclusion, single-dose, oral loading with propafenone or flecainide are acceptable alternatives to conventional drug regimens in selected hospitalized patients. In addition, the measure of a placebo effect is mandatory in studies of recent-onset AF.     

Spectrum of epilepsy and electroencephalogram patterns in Wolf–Hirschhorn syndrome: experience with 87 patients

To define the spectrum of epilepsy in Wolf–Hirschhorn syndrome (WHS) better, we studied 87 patients (54 females, 33 males; median age 5.6 years; age range 1–25.6 years) with confirmed 4p16.3 deletion. On the basis of clinical charts, we retrospectively analyzed the evolution of the electroencephalogram (EEG) findings and seizures. Epilepsy occurred in 81 patients (93%) within the first 3 years of life. Sixty out of 81 (74%) had generalized tonic–clonic seizures, which was the only seizure pattern in 32. Tonic spasms occurred in 15 out of 81 (18%), complex partial seizures in 10 out of 81 (12%), and clonic seizures in 6 out of 81 (7%). Seizures were frequently triggered by fever (59 out of 81; 73%), and occurred in clusters in 36 out of 72 (50%). In the same 36 (50%), unilateral or generalized clonic or tonic–clonic status epilepticus occurred during the first 3 years of life. Twenty-seven out of 81 patients (33%) developed atypical absences between 1 and 6 years, accompanied by a myoclonic component involving the eyelids and the hands. Distinctive EEG abnormalities were observed in 73 out of 81 (90%). Epilepsy was well controlled in 65 out of 81 (81%), mainly with valproate and phenobarbital, and improved with age in all. Thirty-two out of 58 (55%) are currently seizure-free. Seizures stopped at a median age of 4 years 6 months. Epilepsy represents a major clinical challenge in WHS; however, it has a good prognosis. Early diagnosis and treatment of atypical absences, subtle and often misdiagnosed, is mandatory.     

Physiologic Pacing for Atrial Fibrillation Prevention in Sinus Node Disease: Long-Term Results

Background: Physiologic pacing has been demonstrated to be effective in preventing atrial fibrillation recurrences in patients with sinus bradycardia. Aim of the study was to evaluate long-term incidence of atrial fibrillation in a large population of patients affected by sinus node disease receiving physiologic pacing. Furthermore, predictors of arrhythmia recurrence and effect of pacing mode were investigated.
Population: Four hundred twenty-five patients (220 Male, 77 ± 9 years) were retrospectively analyzed: implanted system was AAI in 20.5% and DDD in 79.5%. Thirty-four percent had atrial fibrillation before implant.
Results: Follow-up lasted on average 51 ± 36 months (median 42, range 1 month–18 years). Sixty-six percent were on antiarrhythmic drug therapy. After 5 years, 89% survived, 74.5% had at least one episode of atrial fibrillation, 39.9% were submitted to electrical cardioversion, 67.2% were hospitalized because of cardiac causes, 33.3% developed permanent atrial fibrillation. Primary conduction system disease and valvular heart disease were independent predictors for atrial fibrillation recurrence. Preimplant atrial fibrillation predicted arrhythmia recurrence during the follow-up, but it did not predict development of permanent atrial fibrillation. AAI pacing, when compared with DDD, was associated to a lower rate of atrial fibrillation recurrences (AAI 28.7%, DDD 53.3%, P < 0.001).
Conclusion: In spite of expected benefits of physiologic pacing, the development of atrial fibrillation and permanent atrial fibrillation were quite common. The additional benefits of multifunction pacemakers designed to prevent and treat atrial fibrillation should be evaluated in controlled studies.