What should we do with donated embryos that may be genetically affected?

The ethical and legal issues arising from genetic screening in embryo donation are discussed in relation to two recent cases where embryos with uncertain genetic health were offered for donation.     

Field evaluation of the efficacy and immunogenicity of recombinant hepatitis B vaccine without HBIG in newborn Vietnamese infants

A study involving more than 2,000 infants was conducted in Vietnam to assess the field effectiveness and immunogenicity of recombinant hepatitis B vaccine given at birth, 1 month, 2 months, without concomitant hepatitis B immune globulin (HBIG). All received a 5 microg dose of H-B-VAX II at birth. Infants born to non-carrier mothers (Group 1; N = 1798) then received 2.5 microg doses at 1 and 2 months of age, while infants of HBeAg-negative (Group 2; N = 125) or HBeAg-positive (Group 3; N = 88) carrier mothers received 5 microg doses. No Group 1 or 2 vaccinees were infected. In Group 3, 12 (14.6%) of 82 infants did become infected (estimated efficacy 84%). 98.0-98.6% of uninfected infants who were tested for anti-HBs developed a seroprotective concentration > or = 10 IU/L. In hyperendemic Vietnam, where routine maternal screening and passive-active prophylaxis of high-risk infants with vaccine plus HBIG is not feasible, administration of vaccine alone to all newborns may control effectively HBV infection.     

Diagnosing depression in primary care using self-completed instruments: UK validation of PHQ-9 and CORE-OM.

There is increased emphasis on routine assessment of depression in primary care. This report is the first UK validation of two self-completed measures: the Patient Health Questionnaire (PHQ-9) and the Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM). Optimum cut-off points were established against a diagnostic gold standard in 93 patients. PHQ-9 sensitivity = 91.7% (95% confidence interval [CI] = 77.5 to 98.3%) and specificity 78.3% (95% CI = 65.8 to 87.9%). CORE-OM sensitivity = 91.7% (95% CI = 77.5 to 98.2%) and specificity = 76.7% (95% CI = 64.0 to 86.6%). Brief self-rated questionnaires are as good as clinician-administered instruments in detecting depression in UK primary care.     

Model building on the basis of Dutch cervical cancer screening data

A mass screening programme for cervical cancer is in progress in three pilot regions in The Netherlands. All women living in these regions aged 35-53 are invited to undergo screening at three-year intervals. The MISCAN simulation model was developed for the analysis and optimization of screening programmes. In this paper the model-based approach to evaluation is first outlined and then illustrated by analysing data from the first two screening rounds in the pilot regions. This analysis resulted in a rather restricted range of data-compatible assumptions for the mean duration of preclinical disease (14-19 yr) and the frequency of spontaneous regression of preinvasive lesions (45-65%), as well as a rather wide sensitivity range for the Pap smear (50-90%). These preliminary findings are compared with those of a previous MISCAN analysis of cervical cancer screening in British Columbia. On the basis of an assumed 18-yr duration, 50% regression and 70% sensitivity, a number of screening policies relating to the same age ranges but with different intervals are compared. Both the analysis and the policy comparisons are preliminary, but the findings are nevertheless reasonable and consistent with those of previous studies. A more complete MISCAN-based analysis of the Dutch screening programme and subsequent optimization of screening policies will be possible when further results become available and a cost-effectiveness analysis procedure has been incorporated into the MISCAN programme.     

差异筛选肝癌凋亡细胞cDNA文库的简便方法

目的差异筛选人肝癌凋亡细胞ｃＤＮＡ文库。方法消减杂交和点杂交相结合的噬菌斑原位杂交法筛选ｃＤＮＡ文库，首先采用（－）ｃＤＮＡ探针杂交，挑取（－）的噬菌斑克隆，再用（－）和（＋）两种ｃＤＮＡ探针与初筛出的噬菌斑克隆杂交的差异筛选方法。结果得到４个充分孤立的噬菌斑克隆，其插入片段长度为１．５ｋｂ左右。结论该方法简便、快速，是差异筛选ｃＤＮＡ文库的一种较为可行的简便方法。     

Comparison of screening methods for TEM- and SHV-derived extended-spectrum β-lactamase detection

Objective   To compare common extended-spectrum β -lactamase (ESBL) screening methods and β -lactams for their ability to detect TEM- and SHV-related ESBL enzymes.
Methods   This study compared disk diffusion testing by NCCLS methodology, the Jarlier double disk test, a disk-on-disk test, a modified three-dimensional test and the E test method for their sensitivity and specificity in detecting TEM- and SHV-related ESBL producers. Three negative and 22 positive controls were studied. These were two Klebsiella pneumoniae and 23 Escherichia coli transconjugants. Seventeen β -lactam antibiotics were tested: cefamandole, cefotetan, cefoxitin, cefuroxime, cefixime, cefoperazone, cefotaxime, cefpodoxime, cefsulodin, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, moxalactam, cefepime, cefpirome and aztreonam.
Results   NCCLS disk diffusion was 14% sensitive with ceftriaxone, 36% with cefotaxime, 64% with aztreonam, 68% with cefpodoxime, and 73% with ceftazidime. Cefoperazone, cefamandole, cefpodoxime and cefpirome showed 91% sensitivity using the Jarlier test. Using the disk-on-disk test, cefsulodin showed 95% sensitivity, and cefoperazone, cefepime and cefamandole showed 91% sensitivity. With the modified three-dimensional test, cefoperazone, cefpodoxime and cefpirome showed 91% sensitivity.
Conclusions   For practical reasons, we would recommend use of either the Jarlier test or the commercial cephalosporin disks containing clavulanic acid to screen for ESBL producers. Cefoperazone, cefamandole, cefpodoxime and cefpirome showed good sensitivity across the methods tested.     

Patient and parental attitudes toward genetic screening and its implications at an adult cystic fibrosis centre

General population screening for cystic fibrosis carrier status in the United Kingdom would detect 72% of at-risk couples. Proper counselling would allow these couples to make informed reproductive choices, including the possibility of prenatal diagnosis and the termination of an affected pregnancy. However, children with cystic fibrosis born in this decade, given optimum treatment, now have an average life expectancy of 40 years, and there is no unanimity of opinion on how, where, when, or even if, screening should be offered. The purpose of this questionnaire-based study was to examine the attitudes of an adult clinic population who have grown up with cystic fibrosis, and of their parents, towards genetic screening programmes and the controversies and ethical dilemmas surrounding such programmes in cystic fibrosis. Both patients and parents supported prenatal screening (88% and 90%) and the option of terminating an affected pregnancy (68% and 84%). Only 22% of patients and 10% of parents felt that screening should be limited to families with a history of cystic fibrosis, and 19% and 6%, respectively, that prenatal diagnosis should be restricted to those with a previous child with cystic fibrosis. Despite the negative aspects of any screening programme and the acknowledged ethical problems peculiar to cystic fibrosis, the conclusion of our patients and parents who have lived intimately with the illness is that there should be the option of utilising information available from genetic screening for cystic fibrosis to guide reproductive choices. Pilot programmes to define the optimum management of such screening should continue.     

Comparison of screening methods for detection of extended-spectrum beta-lactamases and their prevalence among Escherichia coli and Klebsiella species in Hong Kong

Three tests, the disk diffusion test, the double-disc synergy test and the inhibitor-potentiated disc diffusion test, were compared for their abilities to detect production of extended-spectrum beta-lactamases (ESBL) in 702 Escherichia coli and 472 Klebsiella spp. strains from four hospitals. Eleven percent E. coli and 13% Klebsiella spp. were found to produce ESBL. As an indicator of ESBL activity, the sensitivities of the five extended-spectrum beta-lactams were as follows: cefotaxime (100%), cefpodoxime (99.3%), ceftriaxone (98.6%), aztreonam (93%) and ceftazidime (57.7%) when interpreted using the National Committee for Clinical Laboratory Standards criteria. Their positive predictive values ranged from 67.8-83.8%. Both the inhibitor-potentiated disc diffusion test and the double-disc synergy test (at three inter-disc widths of 20, 25 and 30 mm) were capable of identifying all the ESBL-producers. However, at a single inter-disc width of 30 mm, the double-disc synergy test has limited sensitivity (83.8%). As a second test for confirming ESBL activity in strains with reduced susceptibility to beta-lactams, the inhibitor-potentiated disc diffusion test is therefore a simple and reliable option.     

69,XXY伴严重生长迟缓及眼球突出病例的产前诊断

目的分析孕中期血清筛查数据和胎儿彩色多普勒与染色体异常之间的关系。方法对一孕中期血清产前筛查18三体风险1:10,血清Free-hCGβ异常减低(值为1.29ng/ml即0.08MOM),胎儿系统结构检查提示胎儿小于孕周,头腹围比(1.63)大于正常(1.25),上唇连续性中断延至鼻底的孕妇进行羊膜腔穿刺,抽取羊水进行细胞遗传学检查。结果羊水细胞染色体核型:69,XXY。结论中孕期妇女血清Free-hCGβ异常减低和胎儿头胸围发育不同步、胎儿唇腭裂提示胎儿染色体畸变可能,血清和超声联合筛查有助于染色体疾病的检出。     

High rate of false positives in blood donor screening for antibodies to hepatitis C virus

Summary Anti-hepatitis C virus antibody screening of blood donors in different countries revealed prevalences ranging from 0,4–1,4%. These results were obtained with an enzyme immunoassay based on a recombinant hepatitis C virus antigen. We applied a specific inhibition assay (neutralization assay) and a recombinant immunoblot assay to determine the specificity of positive reactions in the enzyme immunoassay.Of 2836 blood donor sera tested, 10 (0,35%) were reactive in the enzyme immunoassay, however, only 3 sera (0,1%) proved to be specifically anti-HCV positive in the inhibition assay. The recombinant immunoblot assay gave similar results. The prevalence of anti-hepatitis C virus antibodies among blood donors has been overestimated in recent publications. Furthermore the high rate of false positives in the enzyme immunoassay may explain reports claiming that only a minor part of EIA positive blood units transmitted the hepatitis C virus to recipients.The inhibition assay was also applied to sera of haemophiliacs and of patients with hepatopathy which had reacted positively in the anti-hepatitis C virus antibody enzyme immunoassay. The antihepatitis C virus specificity was confirmed for all sera from the haemophiliacs group (100%) and for 77% of the hepatopathy patients group. Thus, the anti-hepatitis C virus enzyme immunoassay has a high predictive value when it is used to screen groups with high risks of parenteral hepatitis C virus infection, however, its predictive value is very low when it is used for blood donor screening.Abbreviations EIA enzyme immunoassay - HCV hepatitis C virus - RIBA recombinant immunoblot assay - SOD superoxide dismutase