A model to predict long-term sustained response to interferon therapy in chronic hepatitis C

Interferon therapy is used widely for chronic hepatitis C but only a minority of treated patients achieve a long-lasting sustained response. We have developed, by logistic regression, a mathematical model to estimate the probability of sustained response in an individual patient with chronic hepatitis C when treated with interferon-α (IFN-α). The model, which includes age, sex, disease duration, pretreatment serum γ-glutamyl-transpeptidase, alanine aminotransferase and virus genotype, was developed from a database of 307 patients and validated in a new set of 200 patients. It performed well as goodness-of-fit ( P = 0.71 and P = 0.15 in the development and test sample, respectively) and discrimination (area under receiver operating curve = 0.79 in the development and 0.78 in the test sample, respectively). This model may provide decision support in the treatment of chronic hepatitis C with IFN-α.     

幽门螺杆菌尿素酶减毒鼠伤寒杆菌疫苗诱导小鼠粘膜免疫应答的研究

目的:观察口服减毒鼠伤寒杆菌活菌重组疫苗后小鼠的粘膜免疫应答状况。方法:将已构建成功的表达幽门螺杆菌(H.pylori)尿素酶B亚单位(UreB)的重组减毒鼠伤寒杆菌SL3261/pTC01-UreB口服免疫Balb/c小鼠,12周后检测肠液和血清中的特异性抗体反应。结果:疫苗组小鼠的肠液和血清中可分别检测到针对UreB的特异性抗体IgA和IgG,病理学检查显示疫苗组小鼠较对照组小鼠胃粘膜炎症程度差异无统计学意义。结论:表达H.pyloriUreB的减毒鼠伤寒杆菌SL3261/pTC01-UreB能够诱导小鼠产生抗H.pylori的粘膜免疫,可用作抗H.pylori感染的口服疫苗。     

Fentanyl and the interleukin-6 response to surgery

It has been suggested that large doses of opioids may suppress the interleukin-6 response to surgery. We examined the effects of the supplementation of inhalational anaesthesia with either 3 or 15 μg.kg⁻¹ fentanyl on the circulating interleukin-6, interleukin-8, C-reactive protein, cortisol and glucose concentrations in 16 patients undergoing pelvic surgery. In both groups, surgery evoked the expected glucose, cortisol and interleukin-6 response but no increase in interleukin-8 was detected. There were no significant differences between the two groups. We conclude that the supplementation of inhalational anaesthesia with conventional doses of opioids does not modify the cytokine response to surgery.     

5-Hydroxytryptamine increases excitability of CA1 hippocampal pyramidal cells.

In the presence of spiperone to block the 5-HT1A-mediated inhibition of pyramidal cell activity, 5-hydroxytryptamine (serotonin, 5-HT) produces a rapid transient increase in amplitude of the extracellularly recorded population spike from area CA1 of the hippocampus. Intracellular recording techniques in area CA1 of rat hippocampal slices were used to identify the ionic mechanism and to characterize the 5-HT receptor mediating this excitatory response to 5-HT. Most of the experiments were conducted in the presence of spiperone to block the 5HT1A hyperpolarization. Since spiperone also has high affinity for 5-HT2 receptors, any response mediated by 5-HT2 receptors would also be blocked. Bath perfusion of the slice with 5-HT increased the rectification of pyramidal cells in the subthreshold region, increased the resistance, and increased the amplitude of subthreshold excitatory postsynaptic potentials (EPSPs) to initiate spike firing. The 5-HT2,1C-selective agonist DOI mimicked this effect of 5-HT, and the 5-HT2,1C antagonist ketanserin (1 microM) blocked the effect of DOI. There was no change in the amplitude of the slow afterhyperpolarization (sAHP) or the amplitude of evoked inhibitory postsynaptic potentials (IPSPs). The increase in rectification and EPSP amplitude by 5-HT occurred even in the presence of the 5-HT4-selective antagonist BRL 24924 to prevent the decrease in amplitude of the sAHP by 5-HT. We conclude that 5-HT produces a fast excitatory response by increasing subthreshold conductance in CA1 hippocampal pyramidal cells. The identity of the receptor mediating this response was not conclusively identified, but resembled the 5-HT1C receptor.     

Differential Stimulation of Noradrenaline Release by Reversal of the Na+/Ca2+ Exchanger and Depolarization in Chromaffin Cells

We compared the effectiveness of Ca²⁺ entering by Na⁺/Ca²⁺ exchange with that of Ca²⁺ entering by channels produced by membrane depolarization with K⁺ in inducing catecholamine release from bovine adrenal chromaffin cells. The Ca²⁺ influx through the Na⁺/Ca²⁺ exchanger was promoted by reversing the normal inward gradient of Na⁺ by preincubating the cells with ouabain to increase the intracellular Na⁺ and then removing Na⁺ from the external medium. In this way we were able to increase the cytosolic free Ca²⁺ concentration ([Ca²⁺]_c) by Na⁺/Ca²⁺ exchange to 325 ± 14 nM, which was similar to the rise in [Ca²⁺]_c observed upon depolarization with 35 mM K⁺ of cells not treated with ouabain. After incubating the cells with ouabain, K⁺ depolarization raised the [Ca²⁺]_c to 398 ± 31 nM, and the recovery of [Ca²⁺]_c to resting levels was significantly slower. Reversal of the Na⁺ gradient caused an −6-fold increase in the release of noradrenaline or adrenaline, whereas K⁺ depolarization induced a 12-fold increase in noradrenaline release but only a 9-fold increase in adrenaline release. The ratio of noradrenaline to adrenaline release was 1.24 ± 0.23 upon reversal of the Na⁺/Ca²⁺ exchange, whereas it was 1.83 ± 0.19 for K⁺ depolarization. Reversal of the Na⁺/Ca²⁺ exchange appeared to be as efficient as membrane depolarization in inducing adrenaline release, in that the relation of [Ca²⁺]_c to adrenaline release was the same in both cases. In contrast, we found that for the same average [Ca²⁺]_c, the Ca²⁺ influx through voltage-gated channels was much more efficient than the Ca²⁺ entering through the Na⁺/Ca²⁺ exchanger in inducing noradrenaline release from chromaffin ceils. This greater effectiveness of membrane depolarization in stimulating noradrenaline release suggests that there is a pool of noradrenaline vesicles which is more accessible to Ca²⁺ entering through voltage-gated Ca²⁺ channels than to Ca²⁺ entering through the Na⁺/Ca²⁺ exchanger, whereas the adrenaline vesicles do not distinguish between the source of Ca²⁺.     

硬膜外腔阻滞对胸部手术应激反应的影响

目的 观察硬膜外腔阻滞对胸部手术应激激素和细胞因子的影响。方法20例食管癌手术病人,随机分为两组,每组10例,即全麻复令硬膜外腔阻滞(GEA)组和全麻(GA)组,分别测定麻醉诱导前、手术2h、手术4h、术毕、术后1d及术后3d的血浆去甲肾上腺素、肾上腺素、血清促肾上腺皮质激素(ACTH)、皮质醇、C-反应蛋白、IL-6及IL-10的水平。结果 血浆去甲肾上腺素和血清皮质醇GEA组术中术后无显著改变,但GA组术毕和术后1d显著升高(P<0.05),术后3d恢复至术前水平,组间比较前者有显著差异(P<0.05)。两组血浆肾上腺素、IL-10术中术后均无显著变化。两组血清ACTH、IL-6及CRP术中术后均显著升高(P<0.05),组间比较无显著差异。结论 硬膜外腔阻滞可以减轻胸部手术的应激反应。IL-6是较CRP更灵敏的反映组织损伤的炎性指标。     

抗生素C3221-A的分离及结构鉴定

对嗜热放线菌X3221的发酵液进行溶剂萃取、Sephadex LH-20柱分离、中压控纯化,得到一具有抗菌和抗肿瘤活性的抗生素C3221-A。通过理化性质比较和结构单定确定其为Thermorubin A。     

The popularization and application of cold storage red blood cells or whole blood at −80 °C of the Rh(D) negative patients in surgical operation

Summary The efficiency of cold storage red blood cells (CSRBC) or whole blood at −80 °C used in 27 Rh(D) negative patients during surgical operation was reported. The Rh(D) negative patients received the transfusion of CSRBC or whole blood stored at −80 °C for 180 to 360 days. The changes in the indexes, such as blood TB, DB, K⁺, Na⁺, BUN, Cr, urine protein (URPO), UOB, Hb, HCT, serum total protein, relative to hemolytic reaction and blood volume before and after transfusion were observed. The results showed that after transfusion of CSRBC or whole blood 27 cases were negative for urine protein and UOB, and the levels of BUN and Cr were normal (P>0.05). Blood TB, DB, Hb, and HCT were increased, while pH, blood K⁺ and blood Na⁺ was normal with the difference being not significant before and after operation (P>0.05). Plasma protein was decreased, but there was no significant difference before and after operation (P>0.05). It was suggested that CSRBC or whole blood at −80 °C could be safely infused to the Rh(D) negative patients without side effects during the surgical operation. YU Zhongqing, male, born in 1957, Technician in Charge     

Hereditary angio-oedema: new clinical observations and autoimmune screening, complement and kallikrein-kinin analyses

Objectives. To study clinical and laboratory manifestations of hereditary angio-oedema (HAE).
Subjects. Thirty-three affected members of a kindred of 63.
Results. Oedematous attacks in the skin, mucous membranes and gastrointestinal tract with fluid displacement were elicited by mental and physical stress, minor traumas, dental and surgical procedures, eruption of teeth, tonsillitis, pregnancies, and use of oestrogen-containing pills including menopausal substitution. Every adult woman with symptomatic HAE ( n =11) showed symptoms of urinary tract infections in conjunction with the attacks ( P = 0.010), and also experienced more spontaneous abortions or premature labours ( P =0.037) than healthy relatives. Patients with HAE of both sexes more frequently reported heartburn or peptic ulcers ( P =0.002). Rheumatic complaints were reported by 53% of HAE patients and 12% of their unaffected relatives ( P =0.013), but biochemical screening for 18 autoantibodies and quantitation of immunoglobulins did not reveal statistically significant differences between the two groups. C3, prekallikrein, total kininogen, high molecular weight kininogen (HK), alpha-2-macroglobulin and factor XII were not significantly different in HAE patients. In contrast, levels of C1-INH and C4 were depressed and cleaved HK increased in patients compared to unaffected relatives.
Conclusions. HAE manifests in a variety of ways, and may influence risk of spontaneous abortions and premature labour.