Preponderance of β- over α-adrenoceptors in mediating the positive inotropic effect of phenylephrine in the ferret ventricular myocardium

Summary [³H]prazosin bound to the membrane fraction derived from the ferret ventricular muscle with high affinity in a saturable manner (K _d = 0.25 nmol/l and B _max = 27 fmol/mg protein in the right ventricle). [³H]CGP-12177, a -adrenoceptor ligand, bound to the membrane fraction with a _{K d} value of 0.29 nmol/l and a B _max of 42 fmol/mg protein. In the isolated ferret papillary muscle driven at 1 Hz at 37°C, phenylephrine elicited a concentration-dependent positive intropic effect. The maximal effect of phenylephrine was comparable to that of isoprenaline. Prazosin (0.3 ol/l) shifted the concentration-response curve for phenylephrine slightly but significantly to the right, the maximal response being unaffected. In contrast, bupranolol (0.3 gmol/l) shifted the curve for phenylephrine markedly downwards: the maximal response was depressed significantly to 40% and the curve became less steep. In the presence of prazosin and bupranolol the curve was shifted to the right, being essentially parallel to the control curve. These results indicate that in the ferret ventricular myocardium both - and -adrenoceptors mediate the positive inotropic effect of phenylephrine. The extent of contribution of the two classes of adrenoceptor is quite different from that in other mammalian species. In the ferret heart, -adrenoceptors predominate over -adrenoceptors in mediating the positive inotropic effect of phenylephrine, although the number of -adrenoceptors is not especially high when compared with other species. Send offprint requests to M. Endoh at the above address     

Efficacy and tolerability of estraderm MX, a new estradiol matrix patch

Objectives: To assess the efficacy and tolerability of a new matrix patch delivering 0.05 mg estradiol per day (Estraderm MX 50) in postmenopausal women with moderate to severe postmenopausal symptoms. Methods: A multicenter, double-blin, randomized, between-patient, placebo controlled trial in 109 postmenopausal women was carried out. Patches were applied twice weekly for 12 weeks. Patients were assessed at 4, 8 and 12 weeks of treatment. The primary efficacy variable was change from baseline in mean number of moderate to severe hot flushes (including night sweats) per 24 h during the last 2 weeks of treatment. Other variables included Kupperman Index, local and systemic tolerability. Plasma concentrations of estradiol (E2), estrone (E1) and estrone sulfate (E1S) were determined before and after treatment. Results: Estraderm MX was significantly superior to placebo (P < 0.001) in reducing mean number of moderate to severe hot flushes (including night sweats) per 24 h after 4, 8 and 12 weeks of treatment. The estimate of treatment group differences after 12 weeks was 4.2 hot flushes (95% confidence interval: 2.6–5.5). Estraderm MX also significantly reduced Kupperman Index at all time points compared to placebo (P < 0.001). Estraderm MX induced increases in mean E2, E1 and E1S plasma levels as expected (E2: baseline 2.7 pg/ml, 12 weeks 38.9 pg/ml; E1: baseline 18.8 pg/ml, 12 weeks 41.6 pg/ml; E1S: baseline 235.6 pg/ml, 12 weeks 765.1 pg/ml). Overall rates of adverse experiences were similar for Estraderm MX and placebo. The number of patients reporting skin irritation was low and similar in both groups. Conclusions: Estraderm MX 50, a new matrix patch, offers an effective and well tolerated dosage form for transdermal delivery of 0.05 mg E2 per day.     

Thymic stromal cell specialization and the T-cell receptor repertoire

Ten years ago, we proposed a model for thymus function in which thymic epithelial cells are primarily responsible for imprinting major histocompatibility complex (MHC)-restricted specificity, and bone marrow-derived macrophages or dendritic cells are responsible for the induction of self-tolerance. Since then, transgenic and knockout models have allowed for a dissection of thymic stromal components in vivo, leading to a new understanding of their specialized functions. We have determined that with regard to class II-restricted CD4 T-cell development, two distinct subsets of thymic epithelium help shape the repertoire: Cortical epithelium appears solely responsible for positive selection, whereas a fucose-bearing subset of medullary epithelium is specialized for negative selection. This absolute separation of positive and negative selection into two distinct spatial and temporal compartments leads to a much simpler view of the process of repertoire selection. Finally, a novel view of the function of the thymic medulla is discussed.     

筑起抗击"非典"的心理长城

目的 探讨心理疗法对防治SARS的作用,方法 本文综合国内外心理疗法研究成果,提出了应对非典的心理处方：“接纳恐惧,顺其自然;平衡思维,端正认识;积极暗示,增强信心;切已体察,心理常态”;结果 从原理上解释其发生作用的机制,明确心理处方的实际操作,提出具体的步骤和要点,并对日常生活中的不妥做法进行了剖析。结论 采用心理疗法可增强抗击“非典”的信心及提高免疫功能。     

发作间期PET和SPECT检查对颞叶癫痫定位的诊断价值

目的：探讨发作间期１８Ｆ脱氧葡萄糖（ＦＤＧ）正电子发射断层扫描（ＰＥＴ）和９９ｍＴｃ已撑半胱氨酸（ＥＣＤ）单光子发射断层扫描（ＳＰＥＣＴ）对难治性颞叶癫痫（ＴＬＥ）的定位诊断价值。方法：５３例脑电图（ＥＥＧ）定位明确的难治性ＴＬＥ患者分别行发作间期１８ＦＦＤＧＰＥＴ和９９ｍＴｃＥＣＤＳＰＥＣＴ检查。其中２１例磁共振（ＭＲＩ）显示有结构性病变并与ＥＥＧ定位结果一致。结果：ＭＲＩ异常组均在ＰＥＴ和ＳＰＥＣＴ相应部位出现低代谢和低灌注表现。ＭＲＩ正常组，ＰＥＴ定位准确率为８４％，显著高于ＳＰＥＣＴ的５６％（Ｐ＜００５）。结论：对于无结构性病变的颞叶癫痫，发作间期ＰＥＴ检查有较高的定位诊断价值，ＳＰＥＣＴ的临床意义相对较小。     

Psychosocial stress and symptoms of menopause: a comparative study of menopause clinic patients and non-patients

In much of the literature to date, the definition of climacteric symptoms has been based largely upon women who present for medical treatment of symptoms. It is already well recognised that patients (of all ages and both sexes) presenting for medical treatment tend to report themselves as suffering from more life stresses and from more neurotic symptoms than people in the general population. Life stress and adequacy of coping may thus be important factors in the incidence of symptomatology at the climacteric, as at any other time of life. This study therefore investigated the proposal that post-menopausal women who present for treatment at menopause clinics suffer from more life stresses and more neurotic symptoms than post-menopausal women in the general pupolation.

It was found that patients did indeed suffer from more psychosocial stress, measured in terms of life events, clinical depression and anxiety scales and a rating scale based on a clinician's judgements of ongoing psychosocial stress, vulnerability and adequacy of coping. Patients also suffered from significantly more symptoms than non-patients, not only psychological, but also hypothalamic and metabolic symptoms. However, the incidence of hot flushes and vaginal atrophy was the same in both groups. The stress/coping rating was the measure which correlated most highly with the psychological symptoms reported by subjects as symptoms of menopause. Life events and clinical stress measures were more consistently related in the non-patient group, indicating possible intervening variables (such as hormone imbalance) in this relationship in the patient group.     

Small CD4+8+TCRlow thymocytes contain precursors of mature T cells

To evaluate directly the developmental potential of cortical CD4⁺8⁺ thymocytes, highly purified populations of small, nondividing CD4⁺8⁺TCR^low and large, dividing CD4⁺8⁺TCR^high thymocytes from H-2^d mice expressing a transgenic T cell receptor restricted by H-2D^b (major histocompatibility complex class I) molecules were transferred into the thymus of normal, nonirradiated H-2^b recipient mice. The results show that both populations generate CD4^?8⁺ thymocytes under these conditions, thus providing conclusive evidence that small cortical thymocytes do not represent a “dead end” but an important intermediate stage in T cell development.     

Symptoms of illness in late adulthood are related to childhood social deprivation and misfortune in men but not in women

Experiencing adverse life events during childhood may increase vulnerability to physical illnesses and psychological disorders during adulthood. We developed an Early Life Events Questionnaire (ELEQ) with 12 scales and administered it to 92 relatively healthy elderly individuals (29 men and 63 women). A canonical-correlation analysis of the 12 ELEQ scales and physical and psychological symptoms revealed a significant canonical correlation. The results indicate that those who grew up in a family with a harsh climate and whose affiliation needs were not met tended to have more psychological and physical symptoms in old age. Regression analysis revealed that, in men, early life events accounted for 42% of the variance in physical symptoms and 39% in psychological symptoms. No significant relationship, however, was found between ELEQ scales and health outcomes in women. These results suggest that women may be less vulnerable than men to the adverse health consequences of childhood deprivation and other misfortunes.This work was supported by Award SA 325 from the Medical Research Service of the Department of Veterans Affairs.     

一般人群中人格维度与心身症状的相关研究

目的：探讨在健康人群中稳定的人格特点与某一时期心身症状的测量之间的关系。方法：对721名被试施测人格量表（QZPS）和SCL-90，通过回归和相关分析探讨两者之间的关系。结果：严谨、沉稳、决断、淡泊和情绪性等人格因素与SCL-90的因子分数正相关，其它人格因素则与SCL-90的因子分数负相关。控制人格因素间的相关之后，进入每个预测心身症状回归方程的人格因素分别为3-5个,其中严谨、自制、沉稳、重感情和热情的回归系数是正值，其它为负值，表明行事严谨、自我克制以及对人热情和重感情等人格特点与心身症状的出现是一致的。结论：人格维度对心身症状有一定的预测能力。     

Reversal of toxic and non-toxic effects of digoxin by digoxin-specific fab fragments in isolated human ventricular myocardium

Summary The time course of the reversal of toxic and nontoxic effects of digoxin by digoxin-specific antibody fragments (Fab) was measured in isolated human ventricular myocardium. A concentration of 2×10^–6 mol/l digoxin was used to produce positive inotropy followed by mechanical signs of toxicity. After addition of a 1.5-fold higher molar concentration of digoxin-specific Fab, signs of toxicity disappeared within 30 min and digoxin-induced force of contraction decayed with a monoexponential time course with a half-life of 52 min. This rate of decay was almost identical to that observed for the dissociation of the digoxin-(Na⁺+K⁺)-ATPase complex in human heart cell membranes. It is concluded that (a) digoxin-specific Fab are capable of completely removing digoxin from its binding sites, (b) the maximal rate of removal of digitalis glycosides from the (Na⁺+K⁺)-ATPase is limited by the dissociation rate constant, and (c) there is a close correlation between the degree of binding of digitalis glycosides to the (Na⁺+K⁺)-ATPase and the increase in force of contraction.Abbreviation Fab Fragment antibody binding (digitalis antidote)