Pharmacokinetic characteristics and tolerability of a novel intravenous immunoglobulin preparation

In two independent trials 10 and 12 healthy volunteers received the novel intravenous immunoglobulin (IVIG) preparations BT 511 and BT 507, respectively. BT 511 contains 5 g human plasma proteins per 100 ml, more than 95% of which are immunoglobulins of the G class (IgG). BT 507 contains in addition 61 IU antibody against hepatitis B surface antigen (anti-HBs)·ml^–1. In trial I volunteers received 4.0 ml/kg (n+4) and 8.0 ml·kg^–1 (n+6) BT 511 to study the tolerability and the magnitude of the increase in immunoglobulins in plasma as well as their decline over 1 month. After administration of the lower dose, plasma IgG increased from 10.7 to 14.7 g·l^–1 directly after the infusion. Following the 8.0 ml·kg^–1 dose a more pronounced increase from 12.4 to 21.2 g·l^–1 was observed. No adverse events occurred. After 1 month IgG concentrations had almost reached baseline values at 12.2 g·l^–1 in the 4.0 ml·kg^–1 group, but were still significantly increased at 15.2 g·l^–1 after the high dose. There was a linear correlation between the maximal IgG plasma concentration and the subsequent decline of IgG during the 29-day observation period. After administration of BT 507 maximal anti-HBs concentrations of 1778 mU·ml^–1 occurred 1.4 h after termination of the infusion. The terminal elimination half-life was 22.4 days, and total clearance and volume of distribution were determined to be 0.122 ml·min^–1 and 5.41, respectively. The pharmacokinetic parameters calculated for anti-HBs as an indicator of IgG were in accordance with the pharmacokinetic behaviour of native IgG.     

Inhibition of HLA B8-restricted recognition by unrelated peptides: evidence for allosteric inhibition

A panel of synthetic peptides representing human lymphocyte antigen (HLA) B8, other class I and class II restricted T cell epitopes and two B cell epitopes, were all able to compete with recognition of a HLA B8 restricted epitope by a cytotoxic T cell clone. Competition was obtained when the competitor peptides were added either before or after the target epitope. The target epitope also had a slow off rate, implicating allosteric inhibition. The presence of non-specific, allosteric binding sites may interfere with experiments attempting to define immunologically relevant MHC binding specificities.     

Correlation between inflammatory cellular responses and chemotactic activity in bronchoalveolar lavage fluid following intratracheal instillation of nickel sulfate in rats

In a preceding study, we reported that the numbers of macrophages and polymorphonuclear leukocytes (PMN) were increased in bronchoalveolar lavage fluid (BALF) following the intratracheal instillation of nickel sulfate (NiSO₄) in rats. In the present study, BALF chemotactic activities for both macrophages and PMN were measured to investigate if the increases of these inflammatory cells in BALF depend on increases in chemotactic activities in epithelial lining fluid (ELF) of the lung. Both the number of PMN and the PMN chemotactic activity peaked at 2 days post-instillation and they were significantly correlated. However, the PMN chemotactic activity was inversely correlated with concentration of leukotriene B₄ (LTB₄), a well-known chemotaxin. Although PMN were not observed in control BALF, LTB₄ concentration in the control ELF (ca. 5×10^–7 M) was estimated to have a potential to attract PMN chemotactically through a membrane in in vitro migration assay. These results suggest that the presence of LTB₄ in ELF itself does not trigger transpulmonary PMN infiltration. The rat BALF were fractionated by high performance liquid chromatography (HPLC), and PMN chemotactic activity of each fraction was measured. The elution profiles of PMN chemotactic activity showed that there were at least two different chemotaxins in BALF obtained from the NiSO₄-exposed rats. Macrophage chemotactic activity in BALF also peaked at 2 days post-instillation. However, the number of macrophages was not significantly correlated with the chemotactic activity for macrophage in BALF. The HPLC study showed that the macrophage chemotactic substance in the BALF obtained from NiSO₄-exposed rats was different from complement fragment (C5a) and its MW was estimated to be 10 – 12 kD. Received: 1 December 1993/Accepted: 16 March 1994     

冠心病患者血清同型半胱氨酸与叶酸、维生素B12水平的变化

目的 探讨冠心病患者血清同型半胱氨酸(HCY)与叶酸、维生素B12浓度的变化及其相关性。方法 选择84例经冠状动脉造影术证实为冠心病的患者，应用荧光偏振免疫分析法(FPIA)测定血清HCY浓度，离子捕获免疫分析法(ICIA)测定血清叶酸浓度，非均相微粒子酶免疫分析法（MEIA)测定血清维生素B12浓度。结果 冠心病患者血清HCY浓度增高，与正常对照组比较有显著性意义(P＜0．001)，而叶酸、维生素B12浓度则降低，与正常对照组比较有显著性意义(P＜0．001)，以上两种变化呈负相关(P＜0．001)。结论 同型半胱氨酸血症是冠心病的新的独立危险因素，叶酸、维生素B12缺乏可能是诱发高HCY的重要因素。     

Cerebellar nuclear afferents--where do they originate? A re-evaluation of the projections from some lower brain stem nuclei

Summary Cerebellar nuclear afferents from some caudal brain stem nuclei in the cat were studied by means of retrograde transport after implantation of the wheat germ agglutinin-horseradish peroxidase complex in crystalline form in the cerebellar nuclei. The findings give evidence that projections to the cerebellar nuclei from certain nuclei of the reticular formation proper (e.g., from the gigantocellular reticular nucleus) are very modest, while there appears to be no or extremely few cerebellar nuclear afferents from the paramedian reticular, spinal trigeminal, gracile, cuneate and external cuneate nuclei. Previous tracer studies have given evidence that also the pontine and red nuclei send very few, if any, fibres to the cerebellar nuclei. All these brain stem regions are known to project to the cerebellar cortex. This relative lack of mossy fibre collaterals to the cerebellar nuclei is discussed with references to previous literature on the distribution of cerebellar nuclear afferents, and the problem of how the cerebellar nuclei are facilitated is considered.Abbreviations Br.c. superior cerebellar peduncle (brachium conjunctivum) - Br.p. middle cerebellar peduncle (brachium pontis) - C.r. interior cerebellar peduncle (restiform body) - HRP horseradish peroxidase - L left - N.c. cuneate nucleus - N.c.e. external cuneate nucleus - N.c.t. nucleus of corpus trapezoideum - NIA anterior interposed nucleus - NIP posterior interposed nucleus - NL lateral (dentate) nucleus - N.l.l. nuclei of lateral lemniscus - NM medial (fastigial) nucleus - N.m.X. dorsal motor vagal nucleus - N.mes. mesencephalic trigeminal nucleus - N.r.l. lateral reticular nucleus (nucleus of the lateral funiculus) - N.r.p. paramedian reticular nucleus - N.r.t. reticular tegmental pontine nucleus - N V, VI, VII, XII root fibres of cranial nerves - Ol.s. superior olive - P.h. nucleus praepositus hypoglossi - Py pyramid - R right - R.gc. gigantocellular reticular nucleus - R.l. lateral reticular nucleus of Meessen and Olszewski - R.p.c. caudal pontine reticular nucleus - R.pc. parvicellular reticular nucleus - R.v. ventral reticular nucleus - Tr.sp.V. spinal tract of the trigeminal nerve - T.s. solitary tract surrounded by nucleus of solitary tract - V.m. medial vestibular nucleus - WGA wheat germ agglutinin - WGA-HRP wheat germ agglutinin-horseradish peroxidase conjugate - V, VI, VII, X, XII motor nuclei of cranial nerves     

行为干预对慢性乙型肝炎患者健康相关行为影响的研究

目的 观察行为干预对慢性乙型肝炎患者健康行为的影响。方法 将300例慢性乙型肝炎患者作为目标人群进行健康教育，建立目标人群管理档案，进行目标人群健康行为干预，比较教育前后相关行为的改变。结果 慢性乙型肝炎患者8项健康行为和8项危险健康行为有明显改观，差异具有统计学意义（P〈0．01）。结论 通过行为干预，有效地使慢性乙型肝炎患者完全遵从医嘱合理用药，完全依从健康行为，从而减少危险行为的发生。     

Prevalence of hepatitis C virus antibody in an area endemic for hepatitis B virus and human T cell leukaemia virus

To clarify the prevalence of concurrent infection with hepatitis C virus (HCV), hepatitis B virus (HBV) and human T cell leukaemia virus (HTLV), we measured HCV antibody in the population of a district endemic for HBV and HTLV infection. Blood samples were collected in June 1990 from 579 inhabitants of four islands of Uwa Bay in the southwest of Ehime Prefecture in Japan. Anti-HCV antibody against C100-3 protein was detected using an enzyme-linked immunosorbent assay kit (Ortho Diagnostics). Thirteen of the 579 inhabitants (2.2%) were positive for anti-HCV, and this prevalence rate was not significantly different from the frequency of anti-HCV in Tokyo blood donors. A total of 11% (64 of 579) of the subjects were positive for HBsAg and 3.3% (19 of 579) were positive for anti-HTLV. These frequencies of HBsAg and anti-HTLV positivity were distinctly higher than the respective means of Japanese. All anti-HCV positive individuals were negative for HBsAg and anti-HTLV, while 54% (7 of 13) had increased alanine aminotransferase levels. These data suggest that the prevalence of HCV infection is not high even in an area endemic for HBV and HTLV infection.     

病毒感染与小儿短暂性滑膜炎关系的研究

探讨小儿短暂性滑膜炎与病毒感染 ,特别是柯萨奇B组病毒 (CVB)感染的关系。方法 :采用酶联免疫吸附试验 (ELISA)对 16 2例小儿髋关节短暂性滑膜炎患儿静脉血和其中的 2 1例关节腔液进行病毒IgM抗体检测 ,柯萨奇病毒B组 (CVB)阳性者进行血清学分型及病毒分离。结果 :在 16 2例静脉血样本中病毒IgM阳性 6 2例 ,占总检数的 38.2 7% ,CVB -IgM2 6例占 16 .0 5 % ,AdV -IgM 19例占 11.73% ,CMV -IgM 10例占 6 .17% ,RSV -IgM 4例占 2 .4 7% ;在关节腔液中检出 9例CVB阳性 ,血清学分型 8例为CVB3,1例为CVB4 ,并分离出 1例CVB3。结论 :CVB和腺病毒 (AdV)是小儿髋关节短暂性滑膜炎感染的主要病毒 ,而且以CVB3为主。     

拉米夫定阻断乙型肝炎病毒宫内传播的临床探讨

【目的】研究拉米夫定对HBsAg阳性孕妇的乙肝病毒 (HBV)宫内阻断作用。【方法】拉米夫定组 43例 ,孕 2 8周起口服拉米夫定 ,每天 10 0mg至产后 30d。对照组 5 2例 ,未予用药。两组孕妇均于孕 2 8周、分娩前 ,其新生儿于生后 2 4h内免疫接种前抽静脉血检测HBsAg、HBeAg及HBV的定量。【结果】拉米夫定组孕妇HBV的DNA水平显著下降 (P <0 0 5 ) ,其新生儿宫内感染率 (16 3% )明显低于对照组 (32 7% ) ,P <0 0 5。两组孕妇及其新生儿未发现有不良反应。【结论】携带HBV孕妇产前服用拉米夫定可有效减少HBV宫内感染发生率。