Initial multicenter experience with double nucleoside therapy for human immunodeficiency virus infection during pregnancy.

OBJECTIVE: To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications. METHODS: A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV-infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV infection status. RESULTS: For all 39 women, zidovudine (ZDV) therapy was instituted at 13.4 +/- 8.2 weeks, with a second agent (lamivudine [3TC] in 85% of cases) being added at a mean gestational age of 17.6 weeks. Duration of therapy with two agents was 20.6 +/- 10.4 weeks overall, with no women stopping medications because of side effects or toxicity. No significant changes in maternal laboratory values were seen, except for an increase in mean corpuscular volume, over the course of pregnancy. No clinically significant adverse neonatal outcomes were noted, with all but the three preterm newborns leaving hospital with their mothers. Neonatal anemia (hematocrit < 50%) was seen in 62% of newborns, with no children needing transfusion; mild elevations of liver function tests, primarily aspartate aminotransferase, were noted in 58% of newborns tested, though none were clinically jaundiced. Overall rate of neonatal HIV infection was 2.5% (95% confidence interval: 0.1-13.2%). CONCLUSION: Combination antiretroviral therapy during pregnancy with two nucleoside analogs was well-tolerated by mothers and newborns, with no significant short-term toxicities or side effects noted. Surveillance of exposed newborns' hematologic and liver function appears warranted.     

The Marshall R. Urist Young Investigator Award. Orthopaedic applications of gene therapy. From concept to clinic

Gene therapy offers new possibilities for the clinical management of orthopaedic conditions that are difficult to treat by traditional surgical or medical means. To bring the potential of this novel technology into the clinic, a research program was initiated that aimed to identify orthopaedically useful genes and develop methods for delivering them to suitable sites under conditions in which gene expression remains at therapeutic levels for the appropriate periods of time; this program is now 10 years old. Rheumatoid arthritis was selected as the lead disease. Preclinical studies evaluating the local and systemic delivery of numerous different genes by in vivo and ex vivo methods in murine and lapin models led to the development of a human gene therapy protocol for arthritis. In this protocol, a gene encoding the human interleukin-1 receptor antagonist protein is transferred to the metacarpophalangeal joints of female patients with rheumatoid arthritis. The first patient was treated this way in July 1996. This is not only the first orthopaedic application of human gene therapy, but also the first use of gene therapy approved for a nonlethal disease. In addition to providing additional therapeutic options for the treatment of rheumatoid arthritis, the experimental data from this study suggest that gene transfer approaches may improve the treatment of osteoarthritis, the repair of cartilage, ligaments, tendons, menisci, intervertebral discs and bone, and the management of disorders such as osteoporosis and osteogenesis imperfecta. They also show promise as a means for developing novel and improved animal models of orthopaedic diseases. If the current rate of progress continues, wide clinical application of gene therapy in various orthopaedic indications should occur within the next 5 to 10 years.     

Immune responses against SARS-coronavirus nucleocapsid protein induced by DNA vaccine

The nucleocapsid （N） protein of SARS-coronavirus （SARS-CoV） is the key protein for the formation of the helical nucleocapsid during virion assembly. This protein is believed to be more conserved than other proteins of the virus, such as spike and membrane glycoprotein. In this study, the N protein of SARS-CoV was expressed in Escherichia coli DHSalpha and identified with pooled sera from patients in the convalescence phase of SARS. A plasmid pCI-N, encoding the full-length N gene of SARS-CoV, was constructed. Expression of the N protein was observed in COS1 cells following transfection with pCI-N. The immune responses induced by intramuscular immunization with pCI-N were evaluated in a murine model. Serum anti-N immunoglobutins and splenocytes proliferative responses against N protein were observed in immunized BALB/c mice. The major immunoglobulin G subclass recognizing N protein was immunoglobulin G2a, and stimulated splenocytes secreted high levels of gamma interferon and IL-2 in response to N protein. More importantly, the immunized mice produced strong delayed-type hypersensitivity （DTH） and CD^8＋ CTL responses to N protein.     

千层塔中三萜成分的研究

前曾报道自千层塔[Huperzia serrata Thunb.(Trev)=Lycopodium serratum Thunb(Trev.)]中分得具有胆碱酯酶抑制活性的新生物碱——石杉碱甲、石杉碱乙、甲基石杉碱乙及已知生物碱8-deoxyserratinine,serratinine,lycodoline及lycoclavine。为进一步阐明该植物的化学成分,我们对其三萜成分进行了研究。从浙江安吉产的千层塔植物中分到六个石松三萜,其中一个为新化合物,经下述方法推定为serratenediol-21-acetate(Ⅰ)。另五     

国产麻黄的形态组织学研究——Ⅱ.西南主产种及其它种

本文报道我国西南产麻黄——丽江麻黄Ephedra likiangensis Florin、匍枝丽江麻黄E.likiangensis f.mairei(Florin)C.Y.Cheng、藏麻黄E.saxatilis Royle ex Florin、山岭麻黄E.gerardiana Wall、垫状山岭麻黄E.gerardiana Var.congesta C.Y.Cheng、矮麻黄E.minuta Florin和异株矮麻黄E.minuta var.dioeca C.Y.Cheng,以及形态组织特征较特殊的宁夏产斑子麻黄E.lepidosperma C.Y.Cheng、新疆产窄膜麻黄E.lomatolepis Schrenk,西藏产西藏中麻黄E.intermedia var.tibetica Stapf的生药形态组织学研究结果。并根据对国产麻黄的生药形态组织学的系统研究结果,分别编写了各种国产麻黄(包括13种3变种1变型)的生药性状和生药显微特征检索表。     

蜜环菌菌丝体化学成分的研究——Ⅴ.蜜环菌辛素和蜜环菌壬素的分离与鉴定

从人工液体发酵培养的蜜环菌[Armillaria mellea(Vahl.ex Fr.)Quel.]菌丝体的石油醚提取物中,经硅胶柱层析,低压柱层析和制备性薄层层析分离得到两个新的原伊鲁烷型倍半萜芳香酸酯类化合物。命名为蜜环菌辛素(armillarilin)和蜜环菌壬素(armillarinia),根据光谱(UV,IR,~1HNMR,~(13)CNMR和MS)分析,推定它们的化学结构分别为Ⅰ和Ⅱ。     

固相法合成心肌兴奋肽及其类似物

用Boc-和Tos-基团分别保护氨基和侧链胍基,以1%交联度聚苯乙烯二苯甲氨基树脂为载体,用DCC固相法合成肽,HF断裂肽树脂键和去除侧链保护基团,粗产物经高效液相层析纯化,合成了心肌兴奋肽Phe-Met-Arg-Phe-NH_2及其类似物Phe-Pro-Arg-Phe-NH_2,并观察了此二种肽对大鼠血压和心率的影响。     

Neck dissection: past, present and future?

With the exception of distant metastasis, the presence of cervical lymph node metastasis is the single most adverse independent prognostic factor in head and neck squamous cell carcinoma. Surgical removal of metastatic cervical lymph nodes had been attempted during the late nineteenth century, with varying techniques and poor results. A systematic approach to en bloc removal of cervical lymph node disease, described in detail by Jawdyński at the end of the nineteenth century and popularized and illustrated by Crile in the early twentieth century, provided consistent and more effective treatment and forms the basis of our current techniques. The concepts of radical neck dissection, employed extensively by Martin, were followed with almost religious consistency by most head and neck surgeons until the late twentieth century, when the principles of 'functional' neck dissection, developed by Suárez and popularized by Bocca, Gavilán, Ballantyne, Byers and others, led to the acceptance of modified radical neck dissection as treatment for lymph node disease in various stages. More recently, selective neck dissection, involving removal of nodes confined to the levels at greatest risk of metastasis from primary tumours at various sites, has become accepted practice for elective and, in some instances, therapeutic treatment of the neck. In the future, sentinel lymph node biopsy and the use of molecular pathological analyses may be employed to predict the presence of occult cervical disease, thus directing therapy to patients at greatest risk and sparing those without regional metastasis.     

Factors associated with 5-year risk of hip fracture in postmenopausal women

Context  The 329 000 hip fractures that annually occur in the United States are associated with high morbidity, mortality, and cost. Identification of those at high risk is a step toward prevention. Objective  To develop an algorithm to predict the 5-year risk of hip fracture in postmenopausal women. Design, Setting, and Participants  A total of 93 676 women who participated in the observational component of the Women's Health Initiative (WHI), a multiethnic longitudinal study, were used to develop a predictive algorithm based on commonly available clinical features. Selected factors that predicted hip fracture were then validated by 68 132 women who participated in the clinical trial. The model was tested in a subset of 10 750 women who had undergone dual-energy x-ray absorptiometry (DXA) scans for bone mass density assessment. Main Outcome Measure  The prediction of centrally adjudicated hip fracture, measured by the area under the receiver operator characteristic (ROC) curves. Results  During a mean (SD) follow-up of 7.6 (1.7) years, 1132 hip fractures were identified among women participating in the observational study (annualized rate, 0.16%), whereas during a mean follow-up of 8.0 (1.7) years, 791 hip fractures occurred among women participating in the clinical trial (annualized rate, 0.14%). Eleven factors predicted hip fracture within 5 years: age, self-reported health, weight, height, race/ethnicity, self-reported physical activity, history of fracture after age 54 years, parental hip fracture, current smoking, current corticosteroid use, and treated diabetes. Receiver operating characteristic curves showed that the algorithm had an area under the curve of 80% (95% confidence interval [CI], 0.77%-0.82%) when tested in the cohort of different women who were in the clinical trial. A simplified point score was developed for the probability of hip fracture. Receiver operating characteristic curves comparing DXA-scan prediction based on a 10% subset of the cohort and the algorithm among those who participated the clinical trial were similar, with an area under the curve of 79% (95% CI, 73%-85%) vs 71% (95% CI, 66%-76%). Conclusion  This algorithm, based on 11 clinical factors, may be useful to predict the 5-year risk of hip fracture among postmenopausal women of various ethnic backgrounds. Further studies are needed to assess the clinical implication of the algorithm in general and specifically to identify treatment benefits.