Allelic loss on chromosome-13 can preceed histological-changes in head and neck-cancer

Seventy paired tumor and blood samples from patients with upper aerodigestive tract squamous cell carcinoma (UADT SCC) were tested for allelic loss on chromosome 13. Increased loss of heterozygosity (LOH) was observed at 11 of 13 different highly polymorphic microsatellite 'CA' dinucleotide repeat-containing loci. Increasing percent LOH correlated with lymph node metastasis (N Stage) (p=0.016). LOH was also detected in 10 of 16 (63%) informative samples of histologically normal mucosa adjacent to the tumors. These findings demonstrate that allelic loss on chromosome 13 is a frequent event in UADT SCC. Furthermore, these genetic alterations can be detected prior to histological changes in normal mucosa adjacent to these tumors.     

Detection of 5-bromo-2-deoxyuridine incorporated into DNA by labeling strand breaks induced by photolysis (sbip)

A novel method to identify DNA replicating cells is described. In this method DNA strand breaks at sites of incorporation of 5-bromo-2-deoxyuridine (BrdUrd) are induced by photolysis and labeled with digoxygenin- or biotin conjugated dUTP. The reaction is catalyzed by exogenous terminal deoxynucleotidyl transferase. This approach, in conjunction with DNA content analysis by flow cytometry, was applied to studies of the proliferation kinetics of human leukemic HL-60 or MOLT-4 cells during pulse and pulse-chase incubation with BrdUrd. A 30-60 min incubation with BrdUrd led to selective labeling of S phase cells and the progression of a cohort of labeled cells through late S, G2 and G1 was revealed by pulse (30 min) - chase (8 h) labeling with the precursor. The presence of apoptotic cells did not interfere with identification of DNA replicating cells, as the subpopulation of apoptotic cells could be distinguished by low DNA content resulting from extraction of DNA during the procedure. The technique could be applied as well to human breast cancer tissue incubated in vitro with BrdUrd. There is no need for DNA denaturation as is required for the conventional immunocytochemical detection of BrdUrd, which can often impair analysis of the cell phenotype. The SBIP methodology may be uniquely advantageous when there is a need for characterization of the phenotype of proliferating cells, or preservation of some features that would otherwise be destroyed during the step of DNA denaturation.     

An analysis of the outcome of microsurgical and laparoscopic adhesiolysis for infertility

We evaluated 81 women with adnexal adhesions and no male factorwho underwent microsurgical (n = 59) and laparoscopic (n = 22)adhesiolysis for infertility. The cumulative conception ratesfor all 81 patients at 12 and 24 months were 41 and 44% respectively.The impact of the following variables on cumulative conceptionrates for all patients was examined: age, duration of infertility,type of infertility, ovulatory status, presence and stage ofendometriosis, adhesion grade, adnexal status (bilateral orunilateral disease, unilateral tubal absence), history of previoussurgery, history of pelvic inflammatory disease and treatmentmodality (microsurgical versus laparoscopic). The results ofindependent comparisons of subgroups within each of these variablesmay be biased because of the interrelationships between thevariables. To overcome this problem, a stepwise Cox's proportionalhazards regression analysis was employed. Our analysis showedthat the single most significant variable influencing the cumulativeconception rates was the duration of infertility (P < 0.005).For every additional year of infertility, the probability ofpregnancy after adhesiolysis (microsurgical or laparoscopic)was reduced by 20%. Cumulative conception rates at 12 and 24months after microsurgical adhesiolysis were 36 and 40% respectively,while after laparoscopic adhesiolysis they were 57% at 12 and24 months. When imbalances were adjusted between the two treatmentgroups, there was no statistically significant difference betweenthe cumulative conception rates for microsurgical and laparoscopicadhesiolysis.     

Treatment of systemic and renal-limited vasculitic disorders with pooled human intravenous immune globulin

Idiopathic crescentic glomerulonephritis is characterized by an absence of immunohistological evidence of immune deposits, often with evidence of segmental glomerular necrosis. Such pauciimmune crescentic glomerulonephritis is the most common renal manifestation seen in patients with Wegener's granulomatosis, polyarteritis nodosa, and glomerulonephritis associated with other systemic vasculitic disorders (i.e., Churg-Strauss syndrome). Recently, the idiopathic crescentic glomerulonephritides, either in renal-limited form or in association with other systemic vasculitic disorders, were found to have in common a serologic marker, antineutrophil cytoplasmic autoantibodies. These cytoplasmic and perinuclear antineutrophil cytoplasmic autoantibodies are specific for constituents of neutrophil primary granules and monocyte lysosomes. As serologic markers for vasculitic disorders, they are also felt to be directly involved in the pathogenesis of necrotizing vascular injury.In vitro, both perinuclear and cytoplasmic antineutrophil cytoplasmic autoantibodies are capable of causing cytokineprimed neutrophils to undergo degranulation and respiratory burst, releasing toxic oxygen species and lytic enzymes. Antiidiotype antibodies which inhibit antineutrophil cytoplasmic autoantibodiesin vitro, in a V region-dependent manner, are found in pooled humanγ-globulin preparations. Intravenous immune globulin infusionsin vivo have produced dramatic improvements in the necrotizing vascular injury produced by antineutrophil cytoplasmic autoantibodies, and a rapid reduction in these autoantibody levels is seen post-intravenous immune globulin infusion in most patients. The proposed mechanisms of action of intravenous immune globulin in vasculitic disorders include Fc-dependent mechanisms, and F(ab′)₂-dependent mechanisms are likely important. Intravenous immune globulin infusions appear to have an important place in the management of the necrotizing vascular injury. Blinded, randomized, placebo-controlled trials will be necessary to establish definitively intravenous immune globulin as a therapeutic option in vasculitic disorders.     

Microdissection and microcloning of chromosomal alterations in human breast cancer

Summary The recognition of recurring sites of chromosome changes in malignancies has greatly facilitated the identification of genes implicated in the pathogenesis of human cancers. Based especially upon recent studies [1–4], it appears increasingly likely that a subset of recurring chromosome alterations will be recognized in human breast cancer. Currently recognized chromosome changes characterizing breast carcinoma include the recognition of cytologic features of gene amplification (e.g. double minutes [dmins] and homogeneously staining regions [HSRs]) [5–8]. As these and other chromosome regions are implicated in recurring abnormalities in breast cancer, it will become increasingly important to have band-or region-specific genomic libraries and probes in order to facilitate high resolution physical mapping and ultimately to clone breast cancer related genes [9]. Toward this end an important recent development in physical mapping has been the establishment of chromosome microdissection as a rapid and reproducible approach to rapidly isolate and characterize chromosome region-specific DNA, greatly facilitating the initial steps in positional cloning of disease-related genes [10–13]. In this brief report, we will highlight the application of chromosome microdissection to the generation of region-specific probes for both fluorescent in situ hybridization (FISH) and the generation of genomic microclone libraries. Additionally, efforts using this methodology to generate a microclone library encompassing the early onset breast/ovarian cancer (BRCA1) gene will be presented.Presented by Jeffrey M. Trent at the 16th Annual San Antonio Breast Cancer Symposium, San Antonio TX, USA, November 4, 1993; Minisymposium on Molecular Genetics in Breast Cancer.     

K-ras mutation in colorectal carcinomas from singapore

54 sporadic colorectal cancers were analyzed for aberrations in the K-ras oncogene. DNA was extracted from frozen tissues obtained from surgical resection and analyzed for mutations in codons 12, 13 and 61 of the K-ras oncogene using single strand conformation polymorphism analysis (SSCP) and direct sequencing. Point mutations in the K-ras oncogene were found in 26/54 (48%) cases, all of which resulted in amino acid substitutions. No other types of mutations (e.g. insertions or deletions) were found. 4 of the mutations were at codon 12, 22 in codon 13 and only 1 was a codon 61 mutant. G-->A transitions were found to be predominant. A remarkable finding was the high preponderance of (13)Gly-(13)Ser mutations (54%). No correlation was observed between K-ras mutations and tumor location, Dukes' stage, differentiation levels, age or sex of the patient.     

Realizing the meta-analytic potential--a survey of experts

A survey of 99 authors of meta-analyses conducted between 1988 and 1993 was undertaken to identify policies and products that might be helpful in the realization of the procedure's ultimate potential. Although a number of differences were found between medical and social/nonmedically related health scientists, the greatest degree of overall enthusiasm for both groups was observed for the need to educate journal editors and primary researchers regarding information that needs to be reported in an empirical study. The respondents were also in general agreement that a consensus should be developed and disseminated on minimum standards for published meta-analyses. A number of the other proposals were less popular, although an argument is made that some of these have actually come to fruition since the original survey was conducted.     

我国消除丙型肝炎的普通人群HCV检测策略的成本效果分析

目的 分析我国消除丙型肝炎（丙肝）的普通人群HCV检测策略的成本效果,明确最佳成本效果的HCV检测年龄。方法 运用TreeAge pro 2019软件构建决策树马尔科夫模型,以1年为周期,模拟10万名20~59岁各年龄组人群HCV检测和治疗结果,以全社会角度分析策略间比较的成本效果和效益。效果指标为增量成本效果比（ICER）,效益指标为净货币效益（NMB）,以我国2022年人均国内生产总值（85 698元）为意愿支付阈值。通过单因素敏感性分析和概率敏感性分析评估结果可靠性。结果 在20~59岁人群HCV检测有成本效果,在40~49岁年龄组进行HCV检测成本效果最佳。20~59岁年龄组人群HCV检测策略与未HCV检测策略比较,增量成本为161.24元/人,增量效用为0.003 6质量调整寿命年（QALYs）/人,ICER为45 197.26元/QALY,ICER小于意愿支付阈值,具有成本效果。各年龄组人群HCV检测策略与未HCV检测策略比较,ICER为42 055.06~53 249.43元/QALY,NMB为96.52~169.86元/人,其中40~49岁年龄组的ICER最低,NMB最高。单因素敏感性分析结果显示,贴现率、丙肝抗体（抗-HCV）检测成本、人群抗-HCV阳性率和直接抗病毒药物治疗成本对经济学评价影响较大,但改变参数取值,结论不变。概率敏感性分析结果表明模型分析结果稳定。结论 医疗机构探索动员20~59岁普通人群进行HCV检测具有较好的成本效果,以40~49岁年龄组人群的HCV检测成本效果最佳。在我国普通人群中实施HCV检测的“愿检尽检”策略,能降低人群丙肝疾病负担。     

深圳市一孩先天性残疾家庭的二孩同类病研究

本文对深圳市1990～1997年因独生子女先天残疾通过病残儿鉴定再生育二孩的家庭进行调查,并以同期通过鉴定的后天性残疾家庭为内对照,以农村地区一孩先天残疾未经病残儿鉴定生育二孩的家庭为外对照,了解其二孩先天残疾再发情况,尤其是同类病的再发情况,拟对独生子女病残儿医学鉴定和二胎生育指标的审批工作效果进行评价,为优生工作提供依据。研究结果表明,鉴定组一孩先天残疾家庭二孩先天残疾的患病率为5.81％,与广州市1986～1991年情况类似(5.9％),高于外省(辽宁1990～1992年为1.35％)。鉴定组二胎同类病发生率为2.8％,非鉴定组为4.55％,两组比较虽无统计学差异,但病种上却有不同,鉴定组为再发风险低的血友病、先天性共转性内斜视、脑萎缩,而非鉴定组为再发风险高的先天聋哑、进行性肌萎缩。提示病残儿鉴定工作颇有成效,避免了相当一部分遗传病家庭再次生育残疾儿,但某些环节有待进一步完善;对农村一胎先天残疾家庭生育二胎也必须纳入管理范围。