Antigenic variants of rabies virus

Antigenic variants of CVS-11 strain of rabies virus were selected after treatment of virus populations with monoclonal antibodies directed against the glycoprotein antigen of the virus. These variants resisted neutralization by the hybridoma antibody used for their selection. Two independently mutating antigenic sites could be distinguished when five variants were tested with nine hybridoma antibodies. The frequency of single epitope variants in a cloned rabies virus seed was approximately 1:10,000. Animals were not or only partially protected when challenged with the parent virus or with another variant, but were fully protected against challenge with the virus used for immunization. Variants were also detected among seven street viruses obtained from fatal cases of human rabies. Animals immunized with standard rabies vaccine were protected against challenge with some but not all street rabies variants. A comparative antigenic analysis between vaccine strain and challenge virus by means of monoclonal antiglycoprotein antibodies showed a slightly closer degree of antigenic relatedness between vaccine and challenge strain in the combinations where vaccination resulted in protection. It remains unknown, however, whether these apparently minor antigenic differences in the glycoproteins account for the varying degrees of protection. The results of this study clearly indicate that the selection of vaccine strains and the methods used to evaluate the potency of rabies vaccines need to be revised.     

S-fluoxetine in the prophylaxis of migraine: a phase II double-blind randomized placebo-controlled study

S-fluoxetine is the long-acting enantiomer of the racemic antidepressant serotonin reuptake inhibitor. Sixty-five patients needing migraine prophylaxis were recruited into a phase II, double-blind, placeho-controlled trial. After a 1-month placebo run-in, 53 patients met entry criteria with regard to attack frequency and were randomized, 27 to S-fluoxetine and 26 to matching placebo. Three failed to start treatment and there were 17 early discontinuations, 9 from S-fluoxetine, 8 from placebo, at similar times and for similar reasons. The primary efficacy variable was attack frequency and analysis compared decline-from-baseline in the two groups. This was earlier and greater (1.7 attacks/28 days, or 52%) on active therapy than on placebo (1.1 attacks/28 days, or 27%), and statistically significant in month 2 (F=4.93; p =0.033) and month 4 (F=4.55; p =0.04l). As secondary measures of efficacy, migraine-days per month and Patient's Global Impression of Disease Severity coherently reflected the changes in attack frequency. Mean attack severity and acute medication use (doses per attack) were unaltered by either treatment. There were no serious adverse events. Withdrawals for adverse events were four from each group but none was considered causally related. The finding of greater efficacy of S-fluoxetine than of placebo should he interpreted conservatively, since the analysis in the final month was made on only half of the entered patients. It supports progression to phase III evaluation, which was the purpose of the study.     

以血红蛋白为基质的氧载体:我们还在原地吗?

Transfusion 2003年第二期上,Lanzkron及其合作者报道了一例镰刀型细胞病人缺乏6-磷酸-葡萄糖脱氢酶伴有急性胸部综合征,因为宗教信仰而拒绝输注红细胞的案例。改善供氧是治疗急性胸部综合征的主要手段,包括补充O_2、扩张支气管及或输注红细胞。这种病人因多种因素导致组织缺氧:氧交换减少(肺栓塞,因为缺氧加剧了不可逆镰刀型变化的细胞导致的肺血管堵塞,及由缺氧引起的肺血管收缩),O_2运输障碍(贫血)和O_2释放减少(6-磷酸-葡萄糖脱氢酶缺陷导致产生高铁血红蛋白亚基,即:使O_2解离曲线左移,O_2亲和力增加)。在这类病人中,输血治疗可望通过血液稀释减少镰刀型细胞的相对比例(从而减少不可逆镰刀型变化的细胞的凝集能力和血管栓塞程度)及增     

Surveillance for human immunodeficiency virus type 1 group O infections in the United States

BACKGROUND: Reports that the human immunodeficiency virus type 1 (HIV- 1) group O variants are not reliably detected by some commercial diagnostic tests have raised concerns about the sensitivity of existing screening tests, especially with regard to blood safety. Although it is unlikely that these divergent strains are prevalent in North America, systematic, continuous surveillance is needed to monitor the potential spread of HIV variants into that region. STUDY DESIGN AND METHODS: Stored serum samples (n = 1072) from both high- and low-risk population groups at several sites in the United States and Puerto Rico were tested by peptide enzyme immunoassays specific for the prototypic HIV-1 group O strains, MVP5180 and ANT70. RESULTS: None of the 1072 samples examined had peptide reactivity that was consistent with HIV-1 group O infection. CONCLUSION: While no evidence of specific HIV-1 group O (MVP5180 or ANT70) infection was found in this study, the sensitivity of current tests has not been fully evaluated against the wide range of genetic variation of HIV. Therefore, it is important to continue active surveillance for HIV-1 and HIV type 2 strains, to characterize any divergent strains, and to judiciously modify tests to correct for any deficiencies in sensitivity.     

Genotyping of the human platelet antigen systems 1 through 5 by multiplex polymerase chain reaction and ligation-based typing

BACKGROUND: Platelet-specific antibodies may be involved in refractoriness to platelet transfusions, disorders such as neonatal alloimmune thrombocytopenia, and post-transfusion purpura. Genotyping for the major human platelet antigen (HPA) systems HPA-1 through HPA-5 is of considerable help in establishing the diagnoses of these diseases. STUDY DESIGN AND METHODS: A new genotyping method is described. Alleles of all five systems are amplified in a multiplex polymerase chain reaction. Subsequently, aliquots of the amplification products are thermocycled in the presence of a pair of allele-specific oligonucleotide probes and a heat-stable ligase. After heat denaturation, the probes hybridize adjacent to complementary sequences of the amplification product. In a perfect match, the two probes become covalently joined. Detection of the ligation product is performed with an enzyme-linked immunosorbent assay. RESULTS: Complete concordance of genotypes between the ligation-based typing and established genotyping methods was determined in 54 Austrian (HPA-1, -2, -3, and -5) and 56 Japanese (HPA-4) individuals. Ligation-based genotyping of HPA-1 polymorphism using platelet-derived RNA as starting material gave concordant results in all 15 cases tested. CONCLUSION: Multiplex polymerase chain reaction in combination with ligation-based typing allows fast typing of large numbers of platelet donors and screening for critical antigens in pregnant women.     

CHLAMYDIAL INFECTIONS

SUMMARY Chlamydiae are among the most successful bacterial pathogens, and there are few branches of medicine on which chlamydial infection and its sequelae do not impinge. Chlamydia trachomatis is responsible for many million cases of blindness, pelvic inflammatory disease, urethritis, epididymitis, infertility and ectopic pregnancy annually; it also causes lymphogranuloma venereum, reactive arthritis, ophthalmia neonatorum and infantile pneumonia. C. pneumoniae is among the most common causes of community-acquired pneumonia, and recent evidence suggests that it may play a part in the pathogenesis of coronary heart disease. C. psittaci is a highly prevalent zoonotic infection with a wide host range. It is of great economic importance, and causes sporadic but sometimes devastating disease in humans. Most chlamydial infections are subclinical, but even if the initial illness is mild there may be serious long-term sequelae. It is therefore important to identify and treat chlamydial infections in their early stages, but diagnosis usually depends on laboratory tests. Recent trials have shown that single doses of the long-acting macrolide azithromycin are effective in the treatment of genital and ocular C. trachomatis infection, but longer courses of antimicrobials remain the mainstay of treatment for C. pneumoniae and C. psittaci infections.     

ASSESSING DYSPEPSIA IN GENERAL PRACTICE

SUMMARY The value of the symptom pattern in achieving an accurate diagnosis in dyspeptic disease is still controversial. A number of investigators have used it to distinguish those patients who are at a high risk of serious disease (ulcer or cancer) from those who are not. Such findings have important implications for patient management, both in clinical and economic terms.