Molecular prenatal diagnosis of ataxia telangiectasia heterozygosity by direct mutational assays.

Ataxia telangiectasia (AT) is a severe autosomal recessive disease, rare but not infrequent in Italy. Owing to the seriousness of the disease, prenatal diagnosis has been attempted in the past by means of cytogenetic, biochemical, radio-biological and indirect molecular analyses. We performed the first direct molecular prenatal diagnosis of AT on a chorionic villi sample from a 37-year-old woman at the 10th week of pregnancy. She had two previous children suffering AT and two induced abortions. At molecular analysis her affected children were compound heterozygotes for mutations 7792C-->T in exon 55 (from the mother) and 8283delTC in exon 59 (from the father). The prenatal diagnosis was performed by two different operators in double-blind form. Mutation 7792C-->T was studied by restriction enzyme analysis using TaqI. Mutation 8283delTC was screened by heteroduplex analysis. The fetus was heterozygous for the mutation 7792C-->T (confirmed by sequencing). In order to verify the possible contamination by maternal DNA, polymorphic loci HLA-DRB1 and HLA-DQA1, together with microsatellite markers D6S259, D11S2000, D11S29, D11S1778 and D11S2179, were examined. All these loci were informative, showing that the fetus received only one allele from each parent. The heterozygosity for ATM mutation 7792C-->T was confirmed by molecular studies after the birth of a healthy male baby.     

环氧酶-2抑制剂的选择性及安全性

目的：了解环氧酶-2抑制剂的作用特点及其临床的用药安全性。方法：综合国内外一些文献资料,阐述环氧酶-2抑制剂的作用方式,作用特点及分类方法,并通过总结临床研究及药物流行病学的研究报道,对临床用药安全性作了初步评价。结果：环氧酶-2抑制剂通过对环氧酶-2的选择性抑制作用,而起到抗炎镇痛作用。而对环氧酶-1的抑制作用较少或甚少,与传统的非甾类抗炎药相比,减少了胃肠道等的毒副作用。提高了用的安全性。结论：环氧酶-2抑制剂特别是高选择性（特异性）抑制剂,由于安全有效,可望成为继传统非甾类抗炎药后的新一代抗炎镇痛药物。     

速激肽受体拮抗剂对白三烯C4引起的豚鼠心血管反应的抑制作用

iv白三烯C₄(LTC₄)0.8nmol·kg^-1引起麻醉豚鼠血压降低和心脏微血管依文思蓝渗出增加。速激肽NK-1受体拮抗剂CP-96345 (2.06μmol·kg^-1,iv)和NK-2受体拮抗剂SR-48968(1.66μmol·kg^-1,iv)部分抑制心房微血管渗漏(分别为46.6%和37.5%);两药合用可明显抑制LTC₄引起的低血压和心房、心室微血管渗漏(分别为58.1%和54.1%),其作用与白三烯特异性拮抗剂ONO-1078(0.06μmol·kg^-1,iv)相似。结果表明速激肽NK-1和NK-2受体可能参与白三烯引起的低血压和心脏炎症反应。     

杏丁注射液对不稳定型心绞痛患者心电图QT的影响

1临床资料符合WHO诊断标准的不稳定型心绞痛(UAP)患者40(男12,女28)例,平均年龄(58.0±8.2)岁.UAP对照组20(男10,女10)例,平均年龄(56.8±9.4)岁.杏丁组常规应用硝酸酯类、肝素、阿司匹林等药物的同时应用杏丁注射液(贵州益佰制药股份有限公司生产,5 mL/支,每支含银杏总黄酮4.5～5.5 mg,双嘧达莫1.8～2.2 mg)25 mL加50 g/L葡萄糖500 mL,每日1次静滴,共14 d.检查12导联心电图3个心动周期以上算得QTd,为消除心率对QTd的影响,再根据Bazzef公式对QTd进行校正,后取其平均值.QT间期的测量为QRS波群开始至T波结束,不包括U波、双向T波时测量其回到等位线的距离.T波低平不易测量则改为测量V2,V3导联的QT及R-R间期(表1).     

Value and cost-effectiveness of screening blood donors for antibody to hepatitis B core antigen as a way of detecting window-phase human immunodeficiency virus type 1 infections. The HIV Blood Donor Study Group

BACKGROUND: The value of screening donors for antibody to hepatitis B core antigen (anti-HBc) for the prevention of posttransfusion hepatitis has declined markedly. However, anti-HBc screening may still be useful as a surrogate marker for the window period (WP) of human immunodeficiency virus type 1 (HIV-1) infection. STUDY DESIGN AND METHODS: First, the relationship between anti-HBc reactivity and HIV-1 WP infections was examined among 225 donors who had seroconverted to anti-HIV-1 positivity between 1987 and 1990. In addition, data from 1654 HIV-1 seropositive donors were analyzed to characterize the relationship among anti-HBc reactivity, donor demographics, and HIV-1- related risk factors. The yield and cost-effectiveness of anti-HBc for HIV-1 prevention were then projected on the basis of a published decision analysis model. RESULTS: Forty (18%) of 225 HIV-1- seroconverting donors tested anti-HBc-reactive on the donation preceding anti-HIV-1 seroconversion; in contrast, 341 (34%) of 1014 HIV- 1-seropositive donors interviewed tested anti-HBc-reactive (chi-square test; p < 0.001). Anti-HBc reactivity was more common among HIV-1- seropositive donors reporting male-to-male sexual contact (169/360, 47%) and injection drug use (44/83, 53%) than among those with heterosexual contacts known to be HIV-1-positive (31/190, 16%) or transfusion exposure (3/21, 14%) or among females with no identified risk factors (21/124, 17%). The estimates of 18 to 34 percent sensitivity for anti-HBc in detecting HIV-1 WP donations and a current rate of 1 in 676,000 HIV-1 WP donations (after p24 antigen screening) suggest that continued use of anti-HBc screening could result in the transfusion of 5 to 12 fewer HIV-1-infected units per year in the United States, which would add 19 to 48 quality-adjusted years of life for the 3.5 million annual transfusion recipients at a cost of $992,020 to $2,345,000 per quality-adjusted life-year saved. CONCLUSION: The low yield and very poor cost-effectiveness of anti-HBc screening indicate that this test is not an effective screening test for HIV-1 WP donations.     

Assessment of the hemostatic effectiveness of human platelets treated with aminomethyltrimethyl psoralen and UV A light using a rabbit ear bleeding time technique

The photochemical aminomethyltrimethyl psoralen (AMT), in conjunction with UV A light (UVA), has been shown to inactivate human immunodeficiency virus-1 and model viruses in platelet suspensions under conditions that have only a minimal effect on in vitro platelet properties. A rabbit ear bleeding time technique was used to assess the hemostatic effectiveness of human platelet suspensions treated with AMT/UVA. New Zealand White rabbits were made thrombocytopenic by a combination of irradiation and heterologous antirabbit platelet antiserum. Reticuloendothelial function in these rabbits was suppressed by the intravenous administration of ethyl palmitate. The hemostatic function of 1- and 5-day-old human platelet suspensions (14.5% plasma) that had been treated on day 1 with 40 micrograms/mL AMT and 24 kJ/m2 UVA (1 x UVA) was evaluated by measuring microvascular bleeding times after a standard incision. Comparable bleeding times were observed after infusion with both control and AMT/UVA-treated platelets stored for either 1 or 5 days. With the transfusion of AMT/1 x UVA-treated platelets stored for 5 days, the mean (+/- SD) bleeding time was 156.3 +/- 39.2 seconds (n = 10). With untreated platelets (no AMT/no UVA), stored for 5 days, the mean bleeding time was 189.2 +/- 36.4 seconds (n = 10). Neither AMT nor 1 x UVA treatment alone influenced the observed bleeding times. In contrast, the hemostatic effectiveness of human platelet suspensions was diminished if they were exposed to three times the standard UVA dose (72 kJ/m2) on day 1 and stored for 4 more days, regardless of whether AMT was present, with the mean bleeding time increasing to 442.2 +/- 122.6 seconds (n = 15, AMT present) or 396.0 +/- 45.9 seconds (n = 10, AMT absent). These results are consistent with data obtained from in vitro studies and indicate that virucidal AMT/1 x UVA treatment does not influence platelet hemostatic function. However, the final conditions to achieve these results must be carefully controlled.     

人参二醇皂甙和三醇皂甙对兔纹状体ATP酶的影响

本文报道用体外给药法,观察了PDS和PTS对纹状体ATP酶(Na⁺、K⁺-ATP酶,Ca²⁺-ATP酶及M²⁺-ATP酶)的影响。结果发现PDS和PTS对Na⁺,K⁺-ATP酶都有明显的抑制作用,且随PDS和PTS浓度的高低,其抑制作用增强或减弱;对Ca²⁺-ATP酶,PDS在10^-5g/ml时有激活作用,当浓度增高到10^-3g/mL时则转为抑制,而PTS仅为抑制效应;对于Mg²⁺-ATP酶能被PDS所兴奋,而被PTS所抑制。此结果表明PDS和PTS对中枢神经系统的作用,可能与其影响脑内ATP酶有密切的内在联系。     

老年人肺癌150例

临床资料 1990-01／2004-06住院老年人肺癌150(男102例，女48)例，年龄60～90(平均74．5)岁．有吸烟史102例(68％)，其中30a以上吸烟史73例(48．7％)．咳嗽、咳痰、痰带血105例(70％)．无呼吸系统症状25例(16．7％)，于健康体检时发现．以肺外症状住院20例(13％)，表现为上腔静脉综合征、Homer综合征、声音嘶哑、杵壮指(趾)、高血钙等．胸片：肺癌110例；痰中脱落细胞检查98例，     

Time course of detection of viral and serologic markers preceding human immunodeficiency virus type 1 seroconversion: implications for screening of blood and tissue donors

BACKGROUND: Almost all human immunodeficiency virus (HIV) transmission via blood or tissues that has occurred since anti-HIV screening was implemented in 1985 is traceable to blood given after infection but before antibody seroconversion, a time that is referred to as the window period. In this study, the performance of newer assays designed to detect viral and serologic markers soon after infection is assessed, and the reduction in the window period achieved by these assays is estimated. STUDY DESIGN AND METHODS: Three cohort studies of persons at high risk for acquiring HIV infection were identified. These studies included well-controlled HIV type 1 (HIV-1) polymerase chain reaction (PCR) analyses of serial preseroconversion specimens from HIV-1- seroconverting homosexual men or intravenous drug users. Of 81 enrollees with anti-HIV-1 seroconversion documented by a viral lysate anti-HIV-1 enzyme immunosorbent assay (EIA) available in 1989, 13 (16%) had PCR-positive preseroconversion specimens. In the present study, sera from these 13 PCR-positive samples were further tested for anti- HIV by 10 contemporary EIAs and 6 supplemental assays, as well as being tested for plasma p24 antigen and HIV-1 RNA. Preseroconversion sera from 38 HIV-1 DNA PCR-negative cohort participants were also tested by selected anti-HIV EIAs and tested for p24 antigen and HIV-1 RNA. On the basis of these laboratory data and the intervals between blood drawing in all 81 men, the reduction in the preseroconversion window period achieved by these new assays was estimated with a mathematical model developed to analyze seroconversion data. RESULTS: Nine (69%) of the 13 preseroconversion PCR-positive samples had anti-HIV that was detectable by one or more contemporary anti-HIV-1 or anti-HIV type 2 EIA. Supplemental antibody assays were negative on all four EIA-nonreactive preseroconversion samples and negative or indeterminate on a high proportion of the nine EIA-reactive PCR-positive samples. Eight (61%) of the 13 samples were p24 antigen-positive, and 11 (85%) were HIV-1 RNA-positive. The estimated reductions in the window period (relative to the index viral lysate-based anti-HIV EIA) were as follows: contemporary anti-HIV-1/2 EIAs, 20.3 days (95% Cl, 8.0–32.5); p24 antigen and DNA PCR, 26.4 days (95% Cl, 12.6–38.7); and RNA PCR, 31.0 days (95% Cl, 16.7–45.3). CONCLUSION: Recent improvement in the sensitivity of anti-HIV assays has resulted in significant shortening of the preseroconversion window period. Consequently, the incremental reduction in the window period that could be achieved by implementing direct virus-detection assays has diminished significantly.