A breathing lung phantom for 81mKr lung ventilation studies its use in dosimetry and quality control

The construction of a breathing lung phantom that can be used to measure the amount of radioactive gas in the lungs as well as to determine the absorbed dose is described. For a lung ventilation study that consists of 6 views of 300 kents each, an effective dose equivalent of 50 Sv was calculated. The phantom is also suitable for comparison of different generator systems.     

The minimum alveolar concentration of sevoflurane in cats

Eight adult cats of either sex were studied. The minimal alveolar concentration (MAC) for sevoflurane in the cats was found to be 2.58 ± 0.30% (mean ± SD). The ratios of MAC values between sevoflurane and halothane, enflurane and isoflurane in cats were very similar to those ratios found in humans and dogs. This observation suggests that the results of this study are correct and allows us to estimate unknown MAC values for sevoflurane in other species using known MAC values for other anesthetic agents.(Doi M, Yunoki H, Ikeda K: The minimum alveolar concentration of sevoflurane in cats. J Anesth 2: 113–114, 1988)     

Effect of a protein binding change on unbound and total plasma concentrations for drugs of intermediate hepatic extraction

For substances eliminated from blood by the liver, the effect of a change in unbound fraction of drug (fu _b )on steady state total (C _b )and unbound (Cu _b )blood concentrations has hitherto only been considered for the two limiting cases, i.e., at the upper and lower extremes of hepatic intrinsic clearance (CL _int ).For a substance of very low CL _int ,if fu _b changes, C _t will change and Cu _b will remain constant, whereas if CL _int isvery high, Cu _b will change and C _b will remain constant.The present study defines the effects of a change in fu _b on C _b and Cu _b over the whole CL _int range. Computer simulations were undertaken which predicted that, for a given change in fu _b ,absolute and relative changes in C _b would decreasenonlinearly with increasing CL _{int, twhile the relative change in} Cu _{b would} increasewith CL _int .The absolute change in Cu_b would be independent of CL _int .Significant changes in C_b and Cu _{b would be observed at intermediate values of} CL _{int not just at the high and low extremes. These theoretical predictions were investigated experimentally in the isolated perfused rat liver by examining the effects of a change in} fu _{b of sodium taurocholate a substance with intermediate} CL _int (such that at fu _b =0.27,hepatic extraction ratio=0.71) induced by concurrent administration of sodium oleate. Sodium 24- ¹⁴ C-taurocholate (specific activity 52 Ci/mmol) was infused into the reservoir in a recycling system at 30 mol/hr for 105 min (n=6). At 45 min a bolus dose of sodium oleate (50 mmol) was administered to the reservoir, followed by a constant infusion of 143 mmol/hr for 1 hr. Following the administration of oleate, taurocholate fu _{b fell promptly by 55% (0.27–0.12). There was a relative increase of taurocholate} C _{b of 22.7% and a relative decrease in} Cu _{b of 45.4%, in accordance with the simulations (p<0.05). We conclude that important changes in unbound steady-state concentration, the pharmacologically active moiety, can occur upon changes in unbound fraction with compounds of intermediate hepatic intrinsic clearance}.This study was supported by the National Health and Medical Research Council of Australia.     

Prodrugs of 5-Iodo-2′-Deoxyuridine for Enhanced Ocular Transport

Problems associated with the use of 5-iodo-2-deoxyundine (IDU) in the treatment of herpes simplex keratitis can be attributed largely to the polar nature of IDU resulting in its poor permeability across the lipoidal epithelial layer of the corneal membrane. Five aliphatic 5-esters of IDU were synthesized and evaluated as prodrugs for potential use in the treatment of deep ocular infections such as stromal keratitis, iritis, and even retinitis. A parabolic relationship between in vitro corneal membrane permeability and carbon chain length of prodrugs is evident. For a given prodrug, enzymatic hydrolysis proceeded most readily in iris–ciliary body, followed by cornea and aqueous humor. An increase in carbon chain length made the prodrugs more enzymatically labile but more resistant to chemical hydrolysis at pH 7.4 and 34°C. The 5-butyryl ester of IDU exhibited an approximately fourfold increase in aqueous humor IDU concentration relative to IDU at 25 min following instillation of 25-µl 5 mM solutions.     

Control of feeding during saline consumption and fluid deprivation in hamsters

Cellular dehydration induced by water deprivation or hypertonic saline injection reduces feeding in a variety of species. Normal feeding in rats is maintained during isotonic saline consumption by increasing the intake of saline compared to the usual intake of water. Hamsters do not show the spontaneous preference for isotonic saline noted in rats, even after adrenalectomy. In the present investigation, feeding by hamsters was depressed during both isotonic and hypertonic saline consumption compared to the usual feeding with water. Saline intakes did not exceed water intakes under similar conditions. When fluid intakes were elevated by prior fluid deprivation, feeding rates increased at all concentrations of saline after a delay proportional to the osmolality of the solution. Positive 24-hr sodium balances were always associated with saline consumption. Water and hypertonic saline injections reduced feeding, and the fluid loads were excreted very slowly. When hamsters were fluid deprived prior to injections, saline totally suppressed feeding, while water increased feeding compared to sham injected controls. It is concluded that cellular dehydration produces a reduction of feeding in hamsters drinking isotonic or hypertonic saline. Reduced feeding with isotonic saline consumption results from the failure of hamsters to increase their ad lib intake of that solution. The prolonged retention of both sodium and fluid after saline consumption or injection suggests that further saline intake may be inhibited by an expansion of the extracellular space.     

社区人群癫癎患者抗癫癎治疗现状及效果分析

目的：研究社区人群癫痫患者药物治疗现状及影响其效果的主要因素。方法：于2000年在上海市金山朱泾镇采用分层整群抽样完成5万人群的癫痫普查，并对癫痫患者进行药物治疗现状调查和对服药者的血药浓度进行测定。结果：癫痫患病率为3.11%，标化患病率为3.62%。癫痫患者中从未服药者33.1%，曾服药者66.9%，目前正在服药者占35.6%，以单药治疗为主。治疗后显效者51.5%，有效者40.6%，无效或恶化者7.9%。服用单药者显效和有效的比例明显高于服用二种药或三种药的效果。服药者血药浓度在有效范围者，仅占36.1%，其中服用苯巴比妥者血药浓度达标的比例（71.4%），明显高于其他药物。血药浓度在有效范围内的显效率为53.3%，明显高于未达有效范围者的显效率（23.8%）。非条件Logistic回归分析显示与治疗效果有关的主要因素为病程、发作年龄、现年龄、发作频率、教育程度、服药类型、血药浓度等。结论：社区人群癫痫患者接受治疗的比例和服药后血药浓度达有效范围的比例都降低。治疗效果受多种因素影响。     

Restriction site polymorphism at the LPA (Lp(a) apoliprotein; apoliprotein(a)) locus

A restriction site polymorphism in the Lp(a) apolipoprotein gene (the LPA gene) is reported. The basis for the polymorphism is presence or absence of an MspI restriction site that appears to be 3' to the last kringle IV structure of the gene. The "1" gene (presence of the restriction site) has a frequency of 0.316 and the "2" gene (absence of the restriction site) has a frequency of 0.684. Both members of each of 67 monozygotic (MZ) twin pairs had the same genotype and there was Mendelian segregation of the DNA variants in 40 families with a total of 75 children. There was a lower proportion of people with genotype 1-1 in the top quartile than in the 3 bottom quartiles of the population distribution of Lp(a) lipoprotein levels but the difference did not reach statistical significance.     

动态观察PSA和F PSA/PSA对诊断前列腺癌的临床价值

为了评价游离前列腺抗原（F PSA）／前列腺抗原（PSA）比值和PSA动态变化（年变化率）在前列腺癌诊断中的应用价值。本文应用ELISA追踪检测PSA在4～10μg／L范围患者在不同时段内PSA水平，并与正常人进行对照，利用ROC曲线，评价FPSA／PSA比值和PSA年变化率两项指标在前列腺癌诊断时的预示价值。结果表明：前列腺癌患者的FPSA／PSA比值和PSA年变化率与非前列腺癌组之间具有显著性差异（P〈0．001），当FPSA／PSA比值的临床判断值为0．21时，诊断灵敏度为93．5％，特异性为91.4％；当PSA年变化率的临床判断值为0．85％。诊断灵敏度为82．6％，诊断特异性为97．9％。前列腺增生患者FPSA／PSA比值与正常人之间无显著性差异（P〉0．05），而PSA年变化率与正常人比较具有显著性差异（P＜0．001）。提示FPSA／PSA比值和PSA年变化率有助于PSA在4～10μg／L范围的患者前列腺癌的诊断。     

Efficiency of work performance and contraction velocity in isotonic tetani of frog sartorius

Mechanical work, ATP, ADP, PC, free creatine and lactate concentrations were determined on IAA poisoned frog sartorii tetanically stimulated in humidified N, at 10°C in isotonic conditions (0.25 or 0.45 P₀). Tetanus duration was 0.35 s, number of tetani was varied from 0 (rest) to 25 (exhaustion). The mechanical work performed per mole ATP+PC split (W _P ^* ) amounted on the average to 16.7 kJ/mol. It was observed, however, that w _p ^* increased from about 13 to about 24 kJ/mol with decreasing ATP concentration from about 2 (resting value) to about 1 mol/g and that this decrease in ATP was associated with a decrease of the shortening (and relaxation) speed of the muscle to about 30% of the values observed on the first tetanus. It is concluded that the thermodynamic efficiency of muscle contraction, calculated from the ratio of w _P ^* (measured) to the thermodynamic affinity (free energy change) of ATP hydrolysis (estimated) increases from about 0.3 to about 0.5 with decreasing ATP concentration and shortening speed.This work was supported by the Fonds National Suisse de la Recherche Scientifique, Grants 3.332.78 and 3.364.0.82     

Reducing the time of sperm-oocyte interaction in human in-vitro fertilization improves the implantation rate

Human oocyte development was evaluated after a reduced timeexposure to spermatozoa in vitro. A total of 119 patients wereassigned to two study groups in a randomized prospective studyin which each patient‘s oocytes were exposed to spermatozoafor either 1 h (group 1 – 58 patients) or the standard16 h incubation period (group 2 – 61 patients). The fertilizationrate obtained in group 1 was higher than in group 2 (285/393,73%, and 272/410, 66% respectively), suggesting that the spermatozoa-oocyteinteraction occurs within 1 h. This was confirmed in a studyin vitro using fluorescently labelled spermatozoa and normaloocyte-cumulus complexes. Spermatozoa enter the cumulus complexwithin 15 min, traverse the cumulus layer within 3 h, and firstappear in the oocyte cortex at 4 h post-insemination. The incidenceof polyspermy was higher in oocytes exposed to spermatozoa for16 h (3%) than for 1 h (1%). There was no difference in thecleavage rate or morphological characteristics of embryos fromboth study groups. However, when evaluating the timing of embryodevelopment, group 1 generated a significantly higher percentageof four to five cell embryos when compared to group 2 (55 versus39%; P < 0.001), documented at 40 h post-insemination. Theimplantation and pregnancy rates for group 1 were 11 and 28%,while the corresponding rates for group 2 were 8 and 15%. Thissuggests that a reduced exposure of oocyte to spermatozoa favoursembryo viability, possibly due to a decrease in potential damagefrom sperm metabolic waste products.