有限总体抽样及LQAS抽样方法在乡(镇)“四苗”覆盖率评价中的应用

本文应用有限总体抽样和批质量保证抽样方法对浙江省兰溪市三个乡（镇）的儿童计划免疫“四苗”覆盖率进行了现场调查,结果显示样本率与总体率以及两种抽样方法的样本率之间均无显著性差异,上述结果表明,有限总体抽样和批量量保证抽样方法均能反映总“四苗”覆盖率水平,且经济,简便。     

Protein binding of brequinar in the plasma of healthy donors and cancer patients and analysis of the relationship between protein binding and pharmacokinetics in cancer patients

The protein binding of weakly acidic and basic drugs has been shown to be altered in cancer patients. Brequinar is a weakly acidic, low-clearance, and highly protein-bound (>98% bound) antitumor agent. The pharmacokinetic parameters of brequinar are subject to large interpatient variability. This large interpatient variability may be related to brequinar's plasma protein-binding capacity (assuming no change in the intrinsic clearance of the unbound drug). The objectives of this study, therefore, were (a) to characterize brequinar's protein binding in the plasma of healthy donors and cancer patients and (b) to examine the relationships between brequinar's plasma protein binding and its pharmacokinetics in patients. Brequinar protein binding was determined in human serum albumin (HSA) solution, drug-free donor plasma, and brequinar-free, predose plasma samples obtained from a phase I cancer trial. Pharmacokinetic results from this study were used to examine relationships between plasma protein binding and drug disposition. In HSA solution and healthy donor plasma, brequinar's protein binding as determined using spiked samples was concentration-dependent. The unbound brequinar fraction increased by a factor of 3 (from 0.3% to 0.9% free) in 4% HSA solution and by a factor of 4 (from 0.4% to 1.6% free) in donor plasma as the brequinar concentrations increased from 0.1 to 2.3 mM in the HSA solution and from 0.076 to 1.5 mM in the donor plasma. Analysis of brequinar binding characteristics using the binding ratio and Rosenthal binding plots showed that albumin was the primary protein for brequinar binding in human plasma. The addition of various concentrations of ₁-acid glycoprotein to 4% HSA solution did not affect the protein binding of brequinar to HSA. The protein binding determined in the plasma of cancer patients was not quantitatively different, except for variability, from that observed in the plasma of healthy donors. Examination of relationships between the unbound brequinar fraction and pharmacokinetics suggested that plasma protein binding was not a major determinant of brequinar disposition in cancer patients.     

血清Ⅲ、Ⅳ型胶原及板层素对肝纤维化的诊断价值

目的：探索诊断早期肝纤维化的敏感指标。方法：用放射免疫法检测２３６例各型肝病患者血清Ⅲ型胶原（ＴｐｙｅⅢｃｏｌａｇｅｎ,ＰＣⅢ）、Ⅳ型胶原（ＴｐｙｅⅣｃｏｌａｇｅｎ,Ⅳ－Ｃ）和板层素（Ｌａｍｉｎｉｎ,ＬＮ）水平。结果：各类肝病患者血清ＰＣⅢ、Ⅳ－Ｃ和ＬＮ水平随病情进展而逐渐升高。以ＰＣⅢ≥１３５μｇ／Ｌ、Ⅳ－Ｃ≥１３０μｇ／Ｌ为诊断肝纤维化的临界点,其敏感度、特异性、准确率分别达８０％以上。结论：表明ＰＣⅢ、Ⅳ－Ｃ及ＬＮ可作为肝纤维化诊断较为敏感的指标,其中Ⅳ－Ｃ对早期肝纤维化的诊断优于ＰＣⅢ及ＬＮ,对肝癌的诊断有一定意义     

Opioid peptide receptor studies, 11: involvement of Tyr148, Trp318 and His319 of the rat mu-opioid receptor in binding of mu-selective ligands

Previous data obtained with the cloned rat mu opioid receptor demonstrated that the "super-potent" opiates, ohmefentanyl (RTI-4614-4) and its four enantiomers, differ in binding affinity, potency, efficacy, and intrinsic efficacy. Molecular modeling (Tang et al., 1996) of fentanyl derivatives binding to the mu receptor suggests that Asp147, Tyr148, Trp318, and His319 are important residues for binding. According to this model, Asp147 interacts with the positively charged opiate agonist to form potent electrostatic and hydrogen-bonding interactions. In this study, the role of weak electrostatic and hydrogen-bonding "pi-pi" interactions of the O atom of the carbonyl group and the phenyl ring structures of RTI-4614-4 and its four enantiomers with residues Tyr148, Trp318, and His319 were explored via site-directed mutagenesis. Tyr148 (in transmembrane helix 3 {TMH3}), Trp318 (TMH7), and His319 (TMH7) were individually replaced with phenylalanine or alanine. Receptors transiently expressed in COS-7 cells were labeled with [125I]IOXY according to published procedures. Mutation of Tyr148 to phenylalanine reduced the binding affinities of some mu-selective agonists (2-7 fold) but did not alter the affinities of DAMGO, naloxone, and the non-selective opiates etorphine and buprenorphine. In contrast, this mutation significantly increased the binding affinities (decreased the Kd values) of [D-Ala2,D-Leu5]enkephalin, IOXY, and dermorphin. Mutation of Trp318 decreased opioid receptor binding to almost undetectable levels. Substitution of alanine for His319 significantly reduced binding affinities for the opioid ligands tested (1.3- to 48-fold), but did not alter the affinities of naloxone and bremazocine. These results indicate the importance of Tyrl48 and His319 for the binding of fentanyl derivatives to the mu receptor. Functional studies using the mutant receptors will provide additional insight into the mechanism of action of RTI-4614-4 and its four enantiomers.     

State-level variation in Medicare spending

Theoretically, Medicare provides one standard benefit package to all enrollees. But because of State-level variations in populations, service supply, and local practice patterns, national policy changes may have unequal impacts on access and service utilization. Across-the-board policy changes may create hardships in one area while appropriately discouraging use in another area. In this article, the authors describe State-level variations in Medicare enrollees, their insurance coverage, 1995 Medicare and beneficiary spending patterns in aggregate, per capita, and by service, and certain spending patterns for dually eligible beneficiaries. These data are useful for considering the State-level effects of payment reform.     

硫酸二甲酯眼损伤的临床表现及治疗

对我们所遇８例硫酸二甲酯眼部中毒的临床表现及治疗进行分析讨论。眼部中毒主要为酸性烧伤、角膜损害,常同时合并呼吸道症状,重者可合并肝肾损害。治疗以硷性溶液冲洗结膜囊及局部对症为主。     

Gene cloning and sequencing of BmK AS and BmK AS-1, two novel neurotoxins from the scorpion Buthus martensi Karsch.

Based on the known amino acid sequences of BmK AS and BmK AS-1, the gene specific primers were designed and synthesized for 3' and 5' RACE (Rapid Amplification of cDNA Ends). Their partial cDNA fragments obtained by 3' and 5' RACE were cloned and sequenced, and the full length cDNA sequences of BmK AS and BmK AS-1 were then completed by overlapping their two partial cDNA sequences, respectively. The predicted amino acid sequences both consist of 85 amino acid residues including a putative signal peptide of 19 residues and a mature toxin of 66 residues. They are different in 17 amino acid residues, among them 11 residues in the mature toxin. The predicted amino acid sequences of BmK AS and BmK AS-1 were almost consistent with those determined and revised (personal communication), only different in one and two residues at their COO-terminal parts, respectively. Based on the determined cDNA sequences, and using the total DNAs isolated from the scorpion venom glands as a template, the genomic DNAs of BmK AS and BmK AS-1 were also amplified by PCR and sequenced. It showed that no intron was inserted in their open reading frames, while in the exon of signal peptide sequences of other Na+, K+ and Cl- channel toxins from the same scorpion, an intron is usually found. However, the Northern blot hybridization results indicated that the sizes of their mRNA should be around 800 bp. Their extra sequences around 400 bp which might function as an intron should be located at their 5' untranslated regions.     

Molecular characterization of a new excitatory insect neurotoxin with an analgesic effect on mice from the scorpion Buthus martensi Karsch.

Besides the neurotoxins active on mammals, a new excitatory insect selective toxin with a mice analgesic activity was found and purified from the venom of the scorpion Buthus martensi Karsch (BmK) (Ji, Y.H., Mansuelle, P., Terakawa, S., Kopeyan, C., Yanaihara, N., Hsu, K., Rochat, H., 1996. Toxicon 34, 987; Luo, M.J., Xiong, Y.M., Wang, M., Wang, D.C., Chi, C.W., 1997. Toxicon 35, 723.). This peptide (designated as BmK IT-AP) is composed of 72 amino acid residues. Its primary structure was determined by automated Edman degradation of the N-terminal part of the reduced and S-carboxamidemethylated protein and its lysylendopeptidase degraded fragments. Based on the determined sequence, the gene specific primers were designed and synthesized for 3' and 5' RACE (rapid amplification of cDNA ends). Their partial cDNA fragments obtained by 3' and 5' RACEwere cloned and sequenced and the full length cDNA sequence of BmK IT-AP was then completed by overlapping their two partial cDNA sequences. It encodes a precursor of 90 amino acid residues: a signal peptide of 18 residues and a mature peptide of 72 residues which are consistent with the determined protein sequence of BmK IT-AP. The genomic DNA of the peptide was also amplified by PCR from the scorpion genomic DNA and sequenced, which is a first report on the genomic structure of a scorpion toxin specific for insects. Its sequence revealed an intron of 590 bp inserted in the end part of the signal peptide. The peptide caused a fast excitatory contraction paralysis on house fly larvae. Furthermore, the peptide also showed an obvious analgesic effect on mice, as assayed by using a twisting test model. This effect of BmK IT-AP well characterized at molecular level is first reported among the known scorpion insect neurotoxins.     

Tissue potassium,selenium, and iron levels associated with gastric cancer progression

The contents of 10 minor and trace elements in histologically confirmed gastric adenocarcinomas and their corresponding normal gastric mucosal tissues obtained from 39 patients at the time of gastric resection were simultaneously determined by instrumental neutron activation analysis. Specimens were irradiated by reactor neutrons and subsequently subject to direct analysis using a high-resolution HPGe -spectrometer. Univariate analysis revealed that gastric cancer tissues had significantly higher concentrations of Fe, K, Mg, Na, Rb, Se, and Zn than normal gastric mucosal tissues. However, multivariate analysis found that Fe, K, and Se were independent elements that associated with gastric cancer. Upon further evaluation of their clinical significance, we found a high tissue K level was related to lymphatic duct metastasis. High Se tissue levels were linked to intestinal type adenocarcinoma. A positive correlation was found between high Fe levels and vascular involvement. These findings suggest that Fe and K are associated with gastric cancer progression. Se is involved in carcinogenesis of stomach in high-risk areas. The mechanisms that underlie the corresponding pathohistological features deserve further study.     

Tedisamil Attenuates Ventricular Fibrillation in a Conscious Canine Model of Sudden Cardiac Death

BACKGROUND: The electrophysiologic and antifibrillatory properties of tedisamil (KC-8857;3,7-di-(cyclopropylmethyl)-9,9-tetramethylene-3,7-diazabicyclo[3.3.1]-nonane dihydrochloride) were studied in a conscious canine model of sudden cardiac death. METHODS AND RESULTS: Three to five days after surgically induced myocardial infarction (2-hour occlusion of the left anterior descending coronary artery), animals were subjected to programmed electrical stimulation to identify those at risk for ischemia-induced ventricular fibrillation. Sixty minutes after tedisamil (10 mg/kg, administered orally) PES was repeated. Tedisamil increased the ventricular effective refractory period from 106 +/- 6 to 134 +/- 7 ms (P <.05) compared to placebo treatment, which did not alter the ERP (123 +/- 6 to 116 +/- 5 ms). Tedisamil prolonged the QTc interval, from a predrug value of 308 +/- 14 to 327 +/- 14 ms, postdrug. The extent of the surgically induced anterior wall myocardial infarct did not differ between groups, tedisamil, 29 +/- 2%, and placebo, 28 +/- 2% of the left ventricle. CONCLUSIONS: Tedisamil conferred protection against ischemia induced ventricular fibrillation; 7 of 10 tedisamil-treated dogs survived, compared to 4 of 14 surviving in the vehicle treated group (P <.05). Although we observed instances of vomiting and/or diarrhea in several dogs after a single oral administration of tedisamil, the data indicate that oral administration of tedisamil provides protection from ischemia-induced ventricular fibrillation in the postinfarcted conscious canine. The mechanism by which tedisamil achieves its antifibrillatory effect may be related to its ability to prolong the ERP of the ventricular myocardium without altering ventricular conduction velocity.