Impact of a conjugate vaccine on community-wide carriage of nonsusceptible Streptococcus pneumoniae in Alaska

BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive bacterial disease and pneumonia among children. Antimicrobial resistance among pneumococci has increased in recent years and complicates treatment. The introduction of heptavalent pneumococcal conjugate vaccine (PCV7) could reduce acquisition of antimicrobial-resistant pneumococci. METHODS: We obtained 1350 nasopharyngeal swabs for culture from 1275 children aged 3-59 months presenting at 3 clinics in Anchorage, Alaska, during the winters of 2000, 2001, and 2002, as PCV7 was being introduced into the routine immunization schedule. We recorded the frequency of use of antibiotics as well as the dates of doses of PCV7 for enrolled children. We used multivariate logistic regression modeling to identify independent risk factors for overall carriage of pneumococci and carriage of PCV7-type pneumococci, cotrimoxazole-nonsusceptible (COT-NS) pneumococci, or penicillin-nonsusceptible (PCN-NS) pneumococci. RESULTS: The proportion of children who were up-to-date for age, with respect to PCV7 vaccination, increased from 0% in 2000 to 55% in 2002. Carriage of PCV7-type pneumococci decreased by 43% (P<.0001). Risk of carriage of PCV7-type pneumococci was lower in 2002 than in 2000, independent of vaccination status, suggesting an indirect effect of vaccination. Carriage of COT-NS, but not PCN-NS, pneumococci also decreased (38%; P=.02), not only among vaccinated children but also among unvaccinated children without recent use of antibiotics. CONCLUSIONS: Introduction of PCV7 into the routine infant immunization schedule in a community with a high prevalence of antimicrobial-resistant pneumococci appears to reduce transmission of PCV7 vaccine serotypes and COT-NS pneumococci but has no impact on overall carriage of pneumococci or carriage of PCN-NS pneumococci.     

Hereditary Hemolytic Disease Secondary to Glucose-6-Phosphate Dehydrogenase Deficiency: Report of Three Cases with Special Emphasis on ATP Metabolism

1. Three cases of hereditary hemolytic disease secondary to G-6-PD deficiency are described. Two of the cases were first cousins of Scotch-Irish-English descent and the mode of inheritance was believed to be sex-linked.The third case was of Turkish origin; no family studies were availale.

2. The mothers, who were heterozygous for G-6-PD deficiency, showed onlyminimal expression of the defect, which was manifested by a slightly decreasedred cell survival in both mothers and an abnormal methemoglobin reductiontest in one of them.

3. All three cases showed a more pronounced fall in erythrocyte ATP afterincubation with phenylhydrazine than that observed in primaquine-sensitiveNegroes whose red cells were less deficient in G-6-PD.

4. It is suggested that the inability of the G-6-PD-deficient erythrocyte tomaintain adequate levels of ATP may be an important factor in the pathogenesis of the hemolytic process.

Submitted on August 26, 1963 Accepted on October 24, 1963     

Update on Interventions in Saphenous Vein Grafts

Interventions in saphenous vein grafts present some of the most challenging problems in preventing acute complications and limiting restenosis. Available options include repeat bypass surgery, balloon angioplasty, directional atherectomy, transluminal extraction atherectomy, rotational atherectomy, laser angioplasty, and stenting. Stenting appears to provide the best acute and long-term results. Debulking with directional atherectomy prior to stenting may be helpful but its role is unproven. With any device, it is essential to attain the lowest possible residual stenosis with the least amount of manipulation. Complications with vein graft interventions are most commonly related to distal embolization, which occurs most frequently in older vein grafts with diffuse disease, large plaque volume or thrombus, or those with total occlusion. Use of thrombolytics, glycoprotein Ilb/IIIa receptor inhibitors, and thrombectomy devices may be helpful when thrombus is present. Calcium channel blockers may be beneficial when embolization of plaque debris results in slow flow or no-flow during interventions.     

TSC1-mTOR-PLK轴以阶段特异性方式调节从施旺细胞增殖到髓鞘形成的内稳态开关

恰如其分的外周髓鞘形成取决于雪旺细胞增殖与分化进程间的平衡。丝氨酸/苏氨酸激酶(mTOR)整合多种环境因素,是细胞生长、代谢、发挥作用的中枢调节者。本文报道了一种mTOR的负性调节剂——结节性硬化复合体(TSC1),通过控制细胞增殖和髓鞘稳态,建立了雪旺细胞谱系进展和髓鞘形成的阶段依赖性程序。小鼠雪旺细胞祖细胞中TSC1的解离导致mTOR信号通路激活,继而导致雪旺细胞过量增殖,分化受阻,髓鞘形成减少。转录组分析显示,TSC1突变体中的mTOR活化使得polo样激酶(PLK)依赖性通路和细胞周期调节剂上调。弱化mTOR或者对PLK进行药理抑制部分挽救了因TSC1缺失导致的外周神经发育过程中的髓鞘形成减少。相较之下,成年小鼠成熟雪旺细胞中TSC1缺失可导致髓鞘的过度增殖和过度生长。本文的发现提示了TSC1-mTOR-PLK信号轴在控制雪旺细胞的发育过程中,从增殖到分化和髓鞘内稳态中起到的阶段特异性功能。