流行性乙型脑炎减毒活疫苗大面积接种后安全性和流行病学效果的5年观察

目的 考核乙脑减毒活疫苗大面积接种后的安全性和降低乙脑发病率,在乙脑高发区安徽省蒙城和涡阳县进行为期５年（１９９２￣１９９６年）的人群观察。方法 观察对象１￣６岁儿童。１岁初免１针,２岁加强１针。结果 通过５年连续观察共接种乙脑活疫苗３３５９４１人。 表明：①疫苗对小龄儿童接种后近期和５年内均未出现不良反应,表明疫苗是安全的。②当地乙脑平均总发病率有显著性下降,从接种观察前１９８７￣１９９１年的１     

Differential diagnosis of anterior segment cysts by ultrasound biomicroscopy

BACKGROUND: To describe the ultrasound biomicroscopic (UBM) features of anterior segment cysts. DESIGN: A retrospective case series. PARTICIPANTS: One hundred eighteen eyes with anterior segment cysts examined by UBM at The New York Eye and Ear Infirmary between August 1992 and November 1997 were included in this study. INTERVENTION: The authors reviewed demographic and diagnostic data from the medical record including ocular and medical history, age, race, gender, and intraocular pressure. Ultrasound data concerning the type, number, position, and acoustic characteristics of cysts were recorded. The authors then correlated the written, clinical, and UBM characteristics. RESULTS: One hundred eyes (92.6%) had neuroepithelial cysts. Ninety (83.3%) of these had primary neuroepithelial cysts, 10 (9.3%) had cysts associated with uveitis, 7 (6.5%) had implantation cysts, and 1 (0.9%) had a cavitated ciliary body tumor. Neuroepithelial cysts typically were round or ovoid, thin-walled, and echolucent. Of the 90 eyes with primary neuroepithelial cysts, 56 (62.2%) had 3 or fewer cysts; multiple cysts (>3 per eye) were found in 34 eyes (37.8%). The multiple cysts occupied more than 180 degrees in 12 patients (13.3%). Primary neuroepithelial cysts were located at the iridociliary junction (74.2%), pars plicata (14.0%), pars plana (6.8%), and iris (5.0%). Implantation cysts (seven eyes) tended to have thicker walls and two contained a copious, echogenic material. CONCLUSION: The UBM results provide important information regarding location and extent of anterior segment cystic lesions. Ultrasound characteristics may help differentiate between neuroepithelial, implantation, and neoplastic cysts.     

Accuracy of a rapid 10-minute carbon-14 urea breath test for the diagnosis of Helicobacter pylori-associated peptic ulcer disease

Urease in the human gastric mucosa is a marker for infection with Helicobacter pylori (HP), an organism which is associated with peptic ulcer disease. To detect gastric urease, we examined 184 patients (144 males, 40 females; mean age: 49.8±15.6 years) with suspected peptic ulcer disease. Fasting patients were given orally 5 Ci of carbon-14 labelled urea. From each patient only one breath sample was collected in hyamine at 10 min. The amount of ¹⁴C collected at 10 min was expressed as follows: [(DPM/mmol CO₂ collected)/(DPM administered)] × 100 × body weight (kg). The presence of HP colonization was determined by examination of multiple endoscopic prepyloric antral biopsy specimens subjected to culture or a rapid urease test. For the purpose of this study, HP-positive patients were defined as those with characteristic bacteria as indicated by a positive result of either the culture or the rapid urease test; HP-negative patients were defined as those with negative findings on both the culture and the rapid urease test. Of the 184 cases, 99 (53.8%) were positive for HP infection, and 85 (46.2%), negative. The sensitivity and specificity of the rapid 10 min ¹⁴C-urea breath test for the diagnosis of HP-associated peptic ulcer disease were evaluated by a receiver operating characteristic (ROC) curve with a variable cut-off value from 1.5 to 4.5. When a cut-off value of 1.5 was selected, the sensitivity was 100% and the specificity, 83.5%; when a cut-off value of 4.5 was selected, the sensitivity was 54.5% and the specificity, 97.6%. Correspondence to: Chia-Hung Kao     

Insulin resistance in the aged: a quantitative evaluation of in vivo insulin sensitivity and in vitro glucose transport

It has recently been made clear that reduced sensitivity to exogenous insulin can be demonstrated in the course of aging. This phenomenon has been further investigated with the aid of sophisticated techniques, such as the euglycemic clamp, which, when coupled with the measurement of hepatic glucose production, showed that "impaired tissue sensitivity to insulin is the primary factor responsible for the decrease of glucose tolerance in advancing age." Nevertheless, this study did not establish whether such impairment reflects reduced sensitivity (receptor deficiency) or reduced response (postreceptor or receptor plus postreceptor defect), as shown in other diseases. Evidence in favor of the view that receptor deficiency is responsible can be seen in our observation of an approximately 50% reduction in receptors in a study of insulin binding on isolated human fat cells. Two aspects of this question appeared to require further investigation: tissue sensitivity to receptor-saturating insulin concentration (euglycemic clamp at about 1000 microU/mL plasma insulin), and the glucose transport system coupled to the receptor. A decrease in receptors alone should shift the insulin sensitivity curve to the right, both in vivo (euglycemic clamp) and in vitro (glucose transport), with no reduction of the maximum effect. A solution to this question is proposed in the light of a study conducted on young volunteers and subjects over 65 years old.     

Hybrid information provided by the 14C-aminopyrine breath test studies with 14C-monomethylaminoantipyrine in the guinea pig

Summary N-Demethylation of ¹⁴C-aminopyrine (¹⁴C-AP), labelled at the methyl groups of the tertiary amino group, yields H¹⁴CHO and ¹⁴C-monomethylaminoantipyrine (¹⁴C-MMAAP) which also undergoes N-demethylation, however, at a slower rate as measured in hepatic microsomes. As after intraperitoneal application to male guinea pigs of ¹⁴C-AP (75 mg/kg; 50 Ci/kg), exhalation rate of ¹⁴CO₂ declines in a biphasic manner, the hypothesis was tested whether the terminal part might reflect N-demethylation of MMAAP. The application of ¹⁴C-MMAAP (70 mg/kg; 10 Ci/kg), resulted in monophasic curves of ¹⁴CO₂ exhalation rate. Their half lives were, however, longer than terminal half lives obtained after ¹⁴C-AP. Obviously, this terminal phase does not represent ¹⁴CO₂ formation from the metabolite MMAAP only, but ¹⁴C-AP might still contribute to ¹⁴CO₂ production. Confirmation was obtained by HPLC determination of AP and MMAAP in serum after injection of AP. Shortly after injection, high concentrations of AP and low ones of MMAAP were found in blood from the portal vein and systemic circulation. Thus, initial parts of ¹⁴CO₂-exhalation rate curves reflect predominantly AP metabolism whereas later phases provide hybrid information.     

P14~(ARF)蛋白与脑胶质瘤发生发展的相关性研究

目的 :探讨脑胶质瘤中 P14 ARF蛋白表达与不同病理级别脑胶质瘤的相关性。方法 :应用免疫组织化学技术检测 31例不同病理分级脑胶质瘤中 P14 ARF蛋白表达 ,5例正常脑组织为正常对照。结果 :P14 ARF蛋白表达阳性率在低级别 ( 级、 级 )和高级别 ( 级、 级 )脑胶质瘤中分别为 87.5 %、30 .4 3%。该蛋白在低级别和高级别中的表达均具有显著性差异 (P<0 .0 5 )。P14 ARF表达水平与脑胶质瘤病理分级之间呈显著负相关性 (r=- 0 .5 71,P<0 .0 1) ,即随着肿瘤恶性度的升高而降低。结论 :P14 ARF蛋白表达异常可导致细胞周期调控失常和细胞异常增殖 ,加速脑胶质瘤恶性演进。     

Synthesis of 3H and 14C labeled (S)‐3‐(5‐chloro‐2‐methoxyphenyl)‐1,3‐dihydro‐3‐fluoro‐6‐(trifluoromethyl)‐2H‐indol‐2‐one,maxipost™. An agent for post‐stroke neuroprotection

The syntheses of tritium labeled (S)‐3‐(5‐chloro‐2‐[OC³H₃]methoxyphenyl‐1,3‐dihydro‐3‐fluoro‐6‐(trifluoromethyl)‐1H‐indol‐2‐one, and carbon‐14 (S)‐3‐(5‐chloro‐2‐methoxyphenyl)‐1,3‐dihydro‐3‐fluoro‐6‐(trifluoromethyl)‐2H‐[2,3‐¹⁴C₂] indol‐2‐one are reported. The ³H‐labeled compound was prepared in a two‐step synthesis from C³H₃I. The final product was purified via chiral HPLC to yield the desired enantiomer in a 4% radiochemical yield and a specific activity of 60 Ci/mmol. The ¹⁴C‐labeled compound was prepared in a four‐step synthesis from diethyl [carboxylate‐¹⁴C₁,₂] oxalate. The final product was purified via chiral HPLC to yield the desired enantiomer in a 20% radiochemical yield and a specific activity of 28.4 μCi/mg. Copyright © 2002 John Wiley & Sons, Ltd.     

[125I], [127I]‐and [14C]‐Labelling of the GLP‐1‐(7‐37) derivative NN2211

Arg³⁴Lys²⁶(N^ε‐(γ‐L ‐glutamyl(N^α‐palmitoyl)))‐GLP‐1(7‐37) (NN2211) is currently in development as a diabetes type 2 drug. The fatty acid attached to the GLP‐1(7‐37) ensures a long and controlled duration of action. The synthesis of [¹²⁵I]NN2211, [¹²⁷I]NN2211 and [¹⁴C]NN2211 used for preclinical ADME studies are described. NN2211 was iodinated using the lactoperoxidase/hydrogen peroxide method, and [¹⁴C]NN2211 was synthesized in 4 steps by two routes both starting from an α‐protected [U‐¹⁴C]glutamic acid. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of tritium and carbon‐14 labelled NNC 61‐4655: a potent dual‐acting PPARα and PPARγ agonist

The synthesis of the potent dual‐acting PPARα and PPARγ agonist NNC 61‐4655 labelled with tritium and carbon‐14 is reported. Tritium labelled NNC 61‐4655 was obtained in three steps with introduction of tritium through catalytic tritium‐halogen exchange of an aryl bromide precursor. This provided [³H]NNC 61‐4655 in 39% overall radiochemical yield with a specific activity of 49 Ci/mmol. Carbon‐14 labelled NNC 61‐4655 was obtained in five steps starting from bromo[1‐¹⁴C]acetic acid. The synthetic sequence, which included a Horner–Wadsworth–Emmons olefination and a Mitsunobu alkylation, provided [¹⁴C]NNC 61‐4655 in 33% overall radiochemical yield with a specific activity of 57.4 mCi/mmol. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of [14C]ABT‐770, matrix metalloproteinase inhibitor (MMPI), labelled in the phenoxy ring

The MMPI [¹⁴C]ABT‐770 (1) , N‐[(1S)‐1‐[(4,4‐Dimethyl‐2,5‐dioxo‐1‐imi‐dazolidinyl)methyl]]‐2‐[[4′‐(trifluoromethoxy)[1,1′‐biphenyl]‐4‐yl]oxy]ethyl]‐N‐hydroxyformamide was synthesized in 8 steps using 4‐bromophenol‐UL‐¹⁴C (10) as a starting material. The Carbon‐14 label was introduced in one of the metabolically stable biphenyl rings. The key sequence of the synthesis was a three‐step one‐pot reaction in which the hydantoin moiety was introduced, the imine oxidized and further hydrolyzed to get the penultimate precursor to [¹⁴C]ABT‐770 (1) in 56% yield. Copyright © 2003 John Wiley & Sons, Ltd.