Proton MR spectroscopic imaging without water suppression

To improve reproducibility in proton magnetic resonance (MR) spectroscopic imaging in human brain, simultaneous acquisition of the internal water reference and metabolite signals was evaluated. Measurements in healthy volunteers showed that the increase in dynamic range from signal oversampling was sufficient to avoid digitization errors. In addition, use of singular value decomposition techniques and finite impulse response filters proved effective in separating water and metabolite signals and providing estimates of the metabolite concentrations.     

联合VEGF-AON和PDGF-TFO对大鼠脑胶质瘤增殖和细胞凋亡的作用效果

目的观察PDGFB链基因的TFO和VEGF的反义寡核苷酸AON对荷瘤大鼠脑胶质瘤增殖和细胞凋亡的影响。方法所有大鼠均在立体定向导引下行右尾状核区微量灌注20μL生理盐水中含1×106C6胶质瘤细胞。在细胞接种后第8天,实验Ⅰ组原位注射含TFO1·0mg的20μL生理盐水,实验Ⅱ和Ⅲ组则分别原位注射含TFO1·0mg AON0·125mg和TFO1·0mg AON0·250mg的20μL生理盐水。以后每隔72h原位注射相同剂量的药物,共注射3次。对照组仅在相同时间原位注射20μL生理盐水。实验3周时处死所有的大鼠,观察肿瘤的生长情况,流式细胞仪观察PDGFB链基因(PDGF-B)、VEGF、PCNA及细胞凋亡的变化。结果实验Ⅰ组的成瘤抑制率为53·1%,实验Ⅱ组为81·4%,实验Ⅲ组为93·1%,三组肿瘤体积比较差异有统计学意义,P<0·01。TFO对胶质瘤细胞PDGF-B、VEGF和PCNA表达有明显的抑制作用;TFO能使胶质瘤细胞凋亡增加。联合应用TFO和AON能更好地抑制PDGF-B、VEGF和PC-NA的表达,使胶质瘤细胞增殖能力进一步降低,细胞凋亡进一步增加。结论联合应用TFO和AON能更有效地抑制肿瘤生长和细胞增殖,促进胶质瘤细胞凋亡。     

Reduced copy number of DAZ genes in subfertile and infertile men.

OBJECTIVE(S): To determine the copy number and identity of the DAZ genes on the Y chromosomes of infertile patients. DESIGN: Prospective study. SETTING: University medical center. PATIENT(S): One hundred and thirty-nine patients with male factor infertility. INTERVENTION(S): The separate genes were detected by polymerase chain reaction (PCR) digestion assays of sequence family variants in leukocyte DNA and by fluorescence in situ hybridization of interphase nuclei and chromatin fibers.MAIN OUTCOME MEASURE(S): Number of DAZ genes present. RESULT(S): One hundred twenty-nine patients had four genes, 6 patients had two genes, and 4 patients had none. Three patients had a deletion of the two proximal DAZ genes, and three were missing both distal genes. Semen analysis showed a less severe phenotype in patients with only two DAZ genes compared with patients missing all four genes. CONCLUSION(s): In six patients, two different partial deletions were found that were not detected by PCR with conventional markers. One patient with an AZFb deletion appeared to also have a partial AZFc deletion that was not detected by routine PCR. Phenotypic differences between patients with different deletions suggest a dose effect of the DAZ genes.     

Three-dimensional electromechanical mapping: imaging in the operating room of the future

BACKGROUND: Three-dimensional electromechanical mapping has previously been shown to be a clinically important tool for cardiac imaging and intervention. We hypothesized that this technology may be beneficial as an intraoperative modality for assessing cardiac hemodynamics and viability during cardiac surgery. We report here the use of this technology as an imaging modality for intraoperative cardiac surgery. METHODS: The tip of a locatable catheter connected to an endocardial mapping and navigating system is accurately localized while simultaneously recording local electrical and mechanical functions. Thus the three-dimensional geometry of the beating cardiac chamber is reconstructed in real time. The system was tested on 6 goats that underwent acute dynamic cardiomyoplasty and on 5 dogs that underwent left anterior descending (LAD) coronary artery ligation. RESULTS: The electromechanical mapping system provided an accurate three-dimensional reconstruction of the beating left ventricle during cardiomyoplasty. After the wrapping procedure, significant end-diastolic area reduction was noted in the base and mid parts of the heart (948 +/- 194 mm2 vs 1245 +/- 33 mm2, p = 0.021; and 779 +/- 200 mm2 vs 1011 +/- 80 mm2, p = 0.016). The area of the cross-section of the apex did not change during the operation. Acute infarcted tissue was characterized 3 days after LAD ligation by concomitant deterioration in both electrical and mechanical function. CONCLUSIONS: By providing both a clear view of the anatomical changes that occur during cardiac surgery, and an accurate assessment of tissue viability, electroanatomic mapping may serve as an important adjunct tool for imaging and analysis of the heart during cardiac surgery     

不稳定性心绞痛患者血清hs-CRP、TnI、CK-MB的研究

目的探讨不稳定性心绞痛患者血清hs—CRP、TnI、CK—MB变化及测定的临床意义。方法利用乳胶增强免疫比浊法和电化学发光法，对154例健康人群、112例uA患者、68例SA患者检测其血清hs—CRP、TnI和CK—MB的水平。结果UA组hs-CRP、TnI、CK—MB水平明显高于SA组（P〈0．01），更远远高于健康组（P〈O．01），并且sA组此三项检测也明显高于健康组（P〈0．05），UA组和SA组及健康组存在显著差异。结论如果将hs—CRP、TnI、CK—MB联合检测，对冠心病的早期诊断，尤其是对不稳定性心绞痛的早期发现及危险性预测，具有重大的现实意义。     

Clastogenic and aneugenic effects of tamoxifen and some of its analogues in hepatocytes from dosed rats and in human lymphoblastoid cells transfected with human P450 cDNAs (MCL-5 cells)

Tamoxifen and its analogues 4-hydroxytamoxifen, toremifene, 4- hydroxytoremifene, clomifene and droloxifene were tested for clastogenic effects in a human lymphoblastoid cell line (MCL-5) expressing elevated native CYP1A1 and containing transfected CYP1A2, CYP2A6, CYP2E1 and CYP3A4 and epoxide hydrolase and in a cell line containing only the viral vector (Ho1). MCL-5 or Ho1 cells were incubated with 4-hydroxytamoxifen, 4-hydroxytoremifene, clomifene or droloxifene and the incidence of micronuclei estimated. With MCL-5 cells there was an increase in micronuclei with 4-hydroxytamoxifen, 4- hydroxytoremifene and clomifene but not with droloxifene. With Ho1 cells only 4-hydroxytamoxifen and 4-hydroxytoremifene caused an increase in micronuclei. MCL-5 cells were incubated with tamoxifen, 4- hydroxytamoxifen, toremifene, droloxifene, clomifene or diethylstilbestrol (0.25-10 microg/ml) for 48 h and subjected to 3 h treatment with vinblastine (0.25 microg/ml) to arrest cells in metaphase. The incidence of cells with chromosomal numerical aberrations (aneuploidy) was increased in cells treated with tamoxifen, 4-hydroxytamoxifen, toremifene, clomifene and diethylstilbestrol but not droloxifene. The frequency of cells with structural abnormalities (excluding gaps) was increased in cells treated with tamoxifen and toremifene but not 4-hydroxytamoxifen, clomifene, droloxifene or diethylstilbestrol. The clastogenic activities of tamoxifen (35 mg/kg), toremifene (36.3 mg/kg), droloxifene (35.2 mg/kg) and diethylstilbestrol (25 mg/kg) were compared in groups of four female Wistar rats. Each chemical was dissolved in glycerol formal, administered as a single dose by gavage and hepatocytes isolated by collagenase perfusion 24 h later. The cells were cultured in the presence of epidermal growth factor (40 ng/ml) for 48 h, colchicine (10 microg/ml) being added for the final 3 h of incubation. At least 100 chromosomal spreads were examined from each animal for the presence of numerical and structural abnormalities. The incidences of aneuploidy following treatment were: tamoxifen 81%, toremifene 46%, droloxifene 9.6%, diethylstilbestrol 45.7%, vehicle control 5.3%. The incidences of chromosomal structural abnormalities excluding gaps were: tamoxifen 4.3%, toremifene 0.8%, droloxifene 0.5%, diethylstilbestrol 0.8%, control 0.5%. The incidence of chromosomal structural aberrations excluding gaps in the treated animals was not statistically significantly different from controls except in the tamoxifen-treated group. Tamoxifen (35 mg/kg per os) and toremifene (36.3 mg/kg per os) were dosed to rats for 4 weeks and chromosomal spreads made from hepatocytes. The incidences of aneuploidy were: tamoxifen 94%, toremifene 57%, control 6.5%. The incidences of chromosomal aberrations excluding gaps were: tamoxifen 12%, toremifene 1%, control 0.5%. The incidence of tamoxifen-induced chromosomal structural abnormalities was significantly elevated compared with control levels. The results demonstrate that tamoxifen and toremifene are the only two drugs tested in the study that cause chromosomal structural and numerical aberrations in vitro and tamoxifen is the only drug that induces both these effects in rat liver cells stimulated to divide in culture following oral dosing. Since chromosomal mutations require cell division for their manifestation and tamoxifen is the only compound of those tested that causes hyperplasia in the rat liver, chromosomal aberrations and aneuploidy in the rat liver would only be expected to occur following treatment with tamoxifen alone, although aneuploidy could be induced by toremifene in conjunction with a promoter such as phenobarbitone.      

Prognostic significance of diagnostic laparoscopy for spontaneous fertility

OBJECTIVE: To determine the prognostic significance of laparoscopy results for fertility outcome. STUDY DESIGN: Consecutive patients undergoing hysterosalpingography and laparoscopy for subfertility in our department between May 1985 and November 1987 were identified from medical records. The impact of tubal occlusion, hydrosalpinx and adhesions as detected at laparoscopy was studied. Kaplan-Meier curves for the occurrence of spontaneous intrauterine pregnancy were constructed for patients without tubal pathology, with mild tubal pathology (unilateral pathology or adhesions) and with severe tubal pathology (bilateral pathology). Fecundity rate ratios (FRR) were calculated to express the association between findings at laparoscopy and the occurrence of spontaneous intrauterine pregnancy. RESULTS: Of the 200 cases that could be analyzed, 129 (65%) showed no tubal occlusion on laparoscopy, 40 (20%) had unilateral tubal occlusion, and 31 (15%) had bilateral tubal occlusion. Unilateral hydrosalpinx was present in 13 (7%) patients, whereas 19 (10%) patients had bilateral hydrosalpinx. Adjusted FRRs were 0.65 and 0.20 for unilateral and bilateral tubal occlusion, and 0.46 and 0.32 for unilateral and bilateral hydrosalpinx. Peritubal adhesions were detected in 43% of patients and seemed to have no prognostic significance. CONCLUSION: Severe tubal pathology detected at laparoscopy affects fertility prospects strongly. However, since spontaneous intrauterine pregnancies occurred even in patients with bilateral tubal occlusion at laparoscopy, this technique should not be considered the gold standard in the diagnosis of tubal infertility.