High-Density Circumferential Pulmonary Vein Mapping with a 20-Pole Expandable Circular Mapping Catheter

The differentiation of pulmonary vein (PV) electrograms from atrial far-field signals during PV isolation (PVI) for atrial fibrillation (AF) may be difficult. In addition, owing to highly variable PV ostial sizes, current fixed-diameter circular PV mapping catheters may not yield optimal electrograms. We evaluated an expandable, circular 15–25 mm diameter, 20-pole mapping catheter for PV mapping during sustained AF in 25 patients. After selective PV angiography to define the ostial position and size, the catheter was introduced into each PV and withdrawn to the most stable proximal position, with optimal wall contact ensured by progressive loop expansion. At each PV ostium, electrograms recorded at high resolution (HR) were compared with those recorded at a resolution similar to that of a standard 10-pole Lasso catheter. After PVI performed during ongoing AF, the presence of residual far-field potentials (FFP) under both set-ups was compared. We mapped 97 PV, including 4 pairs with common ostia. In the HR recordings, the PV potentials had greater amplitude (0.5 ± 0.1 vs 0.3 ± 0.1 mV, P = 0.001) and fragmentation, whereas left atrial FFP were minimized. After successful isolation of all PV, FFP were observed in 33% of left superior and 28% of left inferior PV on the HR recordings, compared to 66% and 61%, respectively under normal resolution. Catheter stability and optimal wall contact, in combination with HR electrograms can optimize circumferential PV mapping during AF and improve the discrimination of FFP postablation.     

The Inhibitory Effect of Tannins on Lipid Peroxidation of Rat Heart Mitochondria

We induced lipid peroxidation in rat heart mitochondria with ferrous sulphate (FeSO₄₎) and compared the inhibitory effect of various tannins on the peroxidation. Oxygen consumption and malondialdehyde (MDA) formation were used to quantitate the amount of lipid peroxidation, and the free radical scavenger activity of tannins was measured with a diphenyl-ρ-picryl hydrazyl (DPPH) method. Of 25 tannins and related compounds tested, catechin benzylthioether and procyanidin B-2 ben-zylthioether were the most potent in inhibiting lipid peroxidation, with inhibitory effects stronger than that of trolox, a water soluble analogue of vitamin E. The concentrations (IC50) required for catechin benzylthioether and procyanidin B-2 benzylthioether to inhibit oxygen consumption to 50% of control values were 0·85 and 2·0 μm, respectively, while their IC50 values from the inhibition of MDA formation were 0·9 and 1·70 μm, respectively. The IC50 values for catechin and procyanidin B-2 to inhibit oxygen consumption were 34·0 and 11·0 μm. Both compounds were less potent than their benzylthioether derivatives. However, the ability of catechin and procyanidin B-2 to scavenge DPPH were similar to that of their benzylthioether derivatives. We conclude that conjugation with a benzylthioether group enhances the inhibitory effect of tannins on lipid peroxidation, and that the mechanism is not an increase in its scavenger activity.     

Rapid cytotoxicity of human B lymphocytes induced by VH4-34 (VH4.21) gene-encoded monoclonal antibodies, II

We have previously described complement-independent killing of human B lymphocytes by two IgM MoAbs derived from the VH4-34 (VH4.21) gene. Analysis of 17 independently derived VH4-34-encoded MoAbs shows that B cell toxicity is not limited to the two described MoAbs, but is a general property shared by a subset of MoAbs derived from the VH4-34 gene. As observed by two independent microscopy techniques, giant membrane pores were formed on target B cells within 10–15 min of exposure to cytotoxic VH4-34-derived MoAbs. Toxicity by individual MoAb correlated directly to its B cell binding intensity measured by FACS, i.e. stronger the binding greater the killing. Sequence analysis showed that V_H region in germ-line or in near germ-line configuration was necessary but not sufficient for B cell binding. In addition, a particular sequence motif enriched in basic amino acids in the CDR3 may be required to supplement the reactivity mediated by the V_H region of the MoAb molecule. VH4-34-encoded antibodies that fulfil the above sequence requirements have cold agglutinin activity towards the i antigen of cord erythrocytes. In vivo, such anti-i/anti-B cell antibodies are rarely detected in healthy adults, but serum levels are dramatically elevated in selective pathological conditions, such as systemic lupus erythematosus and infectious mononucleosis. This strict regulation may be related to the novel and rapid mechanism of human B cell toxicity demonstrated by antibodies encoded by a single human V_H gene.     

The Application of Non-Default Uncertainty Factors in the U.S. EPA's Integrated Risk Information System (IRIS). Part I: UF L,UF S,and “Other Uncertainty Factors”

The United States Environmental Protection Agency's Integrated Risk Information System (IRIS) includes hazard identification and dose-response assessment values developed by Agency scientists. Uncertainty factors (UFs) are used in the development of IRIS values to address the lack of information in five main areas. The standard UFs account for interspecies uncertainty (UF_A) and intraspecies variability (UF_H). The UF_A addresses uncertainty related to the extrapolation of data from animals to humans, whereas the UF_H addresses variability amongst individuals (i.e., intrahuman). Additional UFs have been employed to account for database incompleteness, extrapolations from a lowest-observed-adverse-effect level in the absence of a no-observed-adverse-effect level (UF_L), and subchronic-to-chronic extrapolation (UF_S). A sixth UF designated as “other uncertainty factors” (UF_O) has also been applied in place of the UF_L to account for uncertainty with the adversity of points of departure obtained using benchmark dose modeling. This review will discuss how UF_L, UF_S, and UF_O have been applied in IRIS assessments, along with the rationale used to describe the choice of UF values that deviate from the standard default of 10.     

POTENTIATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL RESPONSE TO METYRAPONE BY l-DOPA IN ACROMEGALIC PATIENTS

The effects of l -DOPA administration on hypothalamic-pituitary-adrenal function were studied in five normal subjects and in five patients with active acromegaly. In acromegalic patients, oral l -DOPA (500 mg every 4 h for six doses) failed to alter the urinary excretion of 17-hydroxycorticoids (17-OHCS), 17-oxosteroids (17-OS), and tetrahydro-11-desoxycortisol (tetrahydro-comp S). However, when cortisol synthesis was blocked with oral metyrapone, enhancement of excretion of 17-OHCS, 17-OS, and tetrahydro-comp S by l -DOPA became apparent in acromegalic patients but not in the normals. In patients with acromegaly, on the day of metyrapone administration, the mean excretion rates of 17-OHCS, 17-OS, and of tetrahydro-comp S were 8.6 mg, 6.4 mg and 4.1 mg/24 h, respectively. When 500 mg l -DOPA was co-administered with metyrapone, the corresponding values increased significantly (P<0.01) to 14.9 mg, 9.0 mg and 7.7 mg/24 h. This effect of l -DOPA was not observed in the normal subjects. It was concluded that l -DOPA markedly enhanced the hypothalamic-pituitary-adrenal response to metyrapone in acromegalic patients, but not in normal subjects. l -DOPA (or one of its metabolites) probably acts upon a noradrenergic or a dopaminergic system located in the hypothalamus to alter the release of ACTH. The unusual pituitary-adrenal response to l -DOPA in acromegaly may reflect: (1) a supersensitive reaction of the pituitary-adrenal axis to l -DOPA; (2) a paradoxical response of the pituitary-adrenal axis to l -DOPA; or (3) a subtle pituitary-adrenal dysfunction.     

Methylprednisolone Inhibits the Expression of Glial Fibrillary Acidic Protein and Chondroitin Sulfate Proteoglycans in Reactivated Astrocytes

创伤后的神经胶质增生导致硫酸软骨素蛋白聚糖(CSPG)的显著表达,从而抑制轴突生长和再生。甲基强地松龙(MP),一种合成的糖皮质激素,在急性脊髓损伤(SCI)的治疗中有神经保护作用和抗炎效应。但是,MP对于CSPG在活性胶质细胞中的表达的作用尚不清楚。本文用a-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯(AM-PA)诱导星形胶质细胞再活化,用环噻嗪模拟SCI的兴奋性中毒刺激。AMPA治疗后,星形胶质细胞再活化的标志物-胶质纤维酸性蛋白(GFAP)、CSPG神经聚糖和磷酸盐的表达都显著上调。AMPA治疗星形胶质细胞的条件培养液强烈抑制大鼠背根神经节中神经元的轴突生长,但这种作用能被MP的预处理所逆转。此外,MP下调成年SCI大鼠中GFAP和CSPG的表达,对抗RU486的糖皮质激素受体(GR)和GR si RNA能逆转MP对GFAP和神经聚糖表达的抑制作用。这些结果提示,MP能在兴奋性中毒损伤后通过GR介导的星形胶质细胞再活化下调和GSPG表达抑制来改善神经修复,促进轴突生长。     

Colposcopy in microinvasive carcinoma of the cervix—an enigma of diagnosis

Summary. Colposcopy and the complementary roles of cervical cytology and biopsy in the diagnosis of microinvasive carcinoma of the cervix were assessed in 26 patients. The cervical cytology indicated cervical intraepithelial neoplasia in 16 (62%) and invasive carcinoma in 10 (38%) patients. A correct colposcopic diagnosis of microinvasive carcinoma was made in only seven (30%) patients while 12 (46%) were diagnosed as having preinvasive carcinoma and four (15%) as having invasive carcinoma. Atypical vessels, characteristic of invasion, were found in less than a third of patients. Microinvasion, therefore, may not be evident on colposcopy alone. Multiple large biopsies under colposcopic guidance are useful with cone biopsy as a back-up.     

广地龙中促进子宫收缩的成分

本文研究了自广地龙中提出来的一种引湿性、淡黄色針状結晶(含量約0.2%)对平滑肌器官(特别是对子宮)的作用。介紹了該結晶的提取方法。該結晶0.1毫克加入25毫升Locke液中,能使已孕和未孕大鼠或豚鼠离体子宮角紧张度明显升高,0.3毫克可使之呈痙攣收縮状态。按1毫克/公斤給已孕和未孕麻醉家兔靜脉注射后15—30分钟,在位子宮紧张度升高,作用維持1.5—3小时。按8—10毫克/公斤注射,子宮紧张度立卽升高和血压急剧下降到零而死亡。9只慢性子宫瘻家兔靜脉注射(3—6毫克/公斤)或灌胃給药(10—20毫克/公斤)后15—45分钟,子宮收縮明显增强,作用維持1.5—3小时(注射給药)和7小时以上(灌胃給药)。多数实驗家兔在子宮兴奋同时有排便現象。該結晶对家兔在位腸管和大鼠后肢血管均有强烈兴奋作用,但对豚鼠支气管肌作用极弱。当給小鼠靜脉注射时,LD₅₀为38.7毫克/公斤。