微波凝固联合黏膜下氟尿嘧啶注射治疗早期低位直肠癌

目的探讨微波凝固联合黏膜下氟尿嘧啶（5-Fu）注射治疗早期低位直肠癌的适应证和疗效。方法1996年1月～2002年12月对9例早期低位直肠癌采用微波凝固联合黏膜下5-Fu注射，微波治疗后用含5．Fu1．0g的生理盐水100～200ml保留灌肠，1次／d，连续3d，随访其疗效。结果3例微波治疗前CEA增高，微波治疗后CEA下降至正常。术中、术后无出血等并发症。随访至2006年1月，9例全部存活。l例生存3年5个月；1例生存3年8个月；1例1年4个月后肿瘤复发，行Miles手术至今又生存2年9个月；6例生存5年以上，其中1例5年1个月，1例6年3个月，l例6年8个月，1例7年6个月，2例9年。结论微波凝固联合黏膜下5-Fu注射治疗早期低位直肠癌适应于早期、距肛缘7cm以下、肿块型、肿瘤直径0．5～3．0cm或肿瘤〈直肠周径的1／3、病理类型为高分化肿瘤、且患者强烈要求保肛的直肠癌。该方法具有创伤小、费用低和疗效满意等特点。     

US and UK versions of the EQ-5D preference weights: Does choice of preference weights make a difference?

Background Most US studies that estimate EQ-5D index score generally apply the UK preference weights. We compared the validity of a newly-developed US weights to the UK weights for use of EQ-5D as a measure of health-related quality of life. Methods Data were collected from a randomized clinical trial for patients with HIV (n = 1,126) in the US. Convergent validity was examined by comparing Pearson correlations of EQ-5D index scores with the MOS-HIV Health Survey scale scores and Physical and Mental Health Summary (PHS, MHS) scores using the US and UK weights. Known-groups validity of EQ-5D US versus UK index scores was compared using clinical variables (CD4+ cell count and HIV viral load), and the MOS-HIV PHS and MHS. Score changes in the EQ-5D index from baseline to week 50 were examined using effect size (ES) estimates. Results The mean EQ-5D index scores was slightly higher using US weights than UK weights (0.87 vs. 0.84, respectively). The correlation coefficient for EQ-5D utilities using the US and UK weights was 0.98. The correlations of EQ-5D index scores with the MOS-HIV scores were moderate and similar using the US and UK weights. The EQ-5D index scores discriminated equally well for both versions between levels of CD4+ count, HIV viral load, and PHS and MHS scores (P < 0.05), suggesting equivalent known-groups validity. The changes in EQ-5D index scores from baseline to week 50 were similar for both versions (ES: 0.21 vs. 0.22 for US and UK, respectively), suggesting equivalent responsiveness to score changes. Conclusions EQ-5D index scores generated using UK and US preference weights showed equivalent psychometric properties. For assessing treatment benefit in a single population, the use of either the UK or US weights as a measure of HRQOL will not change inferences. However, for comparisons across US and UK populations, the choice between these two weights should be based on their relevance to the study population.     

Lithium increases slow wave sleep: possible mediation by brain 5-HT2 receptors?

The effect of lithium on slow wave sleep (SWS) was studied in ten normal male volunteers using home based cassette sleep recording and automatic sleep stage analysis. Lithium increased SWS, an effect consisten with a reduction in brain 5-HT₂ receptor function.     

Synthesis of 14C‐labeled piperidines and application to synthesis of [14C]SCH 351125, a CCR5 receptor antagonist

1‐Benzyl‐4‐hydroxy[2‐¹⁴C]piperidine, a useful intermediate in labeled compound synthesis, was prepared from [¹⁴C]formaldehyde in high yield. The distribution pattern of ¹⁴C in the product is consistent with a mechanism involving reversible iminium ion formation and rapid equilibration of the iminium ion through a cationic aza‐Cope rearrangement. These steps precede the rate‐determining intramolecular cyclization step. SCH 351125 is a potent, selective CCR5 receptor antagonist with potential as a treatment for HIV infection. [¹⁴C]SCH 351125, required for metabolism studies, was prepared from 1‐benzyl‐4‐hydroxy[2‐¹⁴C]piperidine in six steps. [¹⁴C]SCH 351125 is a mixture of four atropisomers. Preparation of [¹⁴C]SCH 351125 besylate salt of the desired atropisomer pair is also described. Copyright © 2007 John Wiley & Sons, Ltd.     

Effect of 5-Aminoisoquinolinone on the Adhesion of Colon Carcinoma

Objective： 5-Aminoisoquinolinone, a water-soluble, potent inhibitor of the activity of poly （adenosine 5＇-diphosphate ribose） polymerase, plays an important role in the tissue injury associated with ischaemia-reperfusion injury and inflammation by inhibiting the activity of poly （adenosine 5＇-diphosphate ribose） polymerase and the expression of cell adhesion molecules such as ICAM-1, P-selectin et al. But how about it in the tumor is not clear. The aim of the present study was to study the effects of 5-Aminoisoquinolinon on the adhesion of colon carcinoma line HT-29 cells to human umbilical vein endothelial cells; and the effects of 5-Aminoisoquinolinon on the expression of ICAM-1, P-selectin and the activity of poly （adenosine 5＇-diphosphate ribose） polymerase in colon carcinoma HT-29 cells. Methods： The adhesion of HT-29 cells to human umbilical vein endothelial cells was detected by adhesive experiment. Immunocytochemically Streptavidin-Peroxidase method was used to investigate the expression of ICAM-1, P-selectin and Poly （adenosine 5＇-diphosphate ribose）（ the product of poly （adenosine 5＇-diphosphate ribose） polymerase activation）. Results： the results of the adhesion assay of HT-29 cells to HUVEC showed that the OD570 value in each 5-AIQ-treated group was significant lower than that in the control group （5-AIQ-untreated） in a dose-dependent manner. The expression of ICAM-1, P-selectin and Poly （adenosine 5＇-diphosphate ribose） was significant lower in 5-Aminoisoquinolinone-treated HT-29 cell group than that in 5-Aminoisoquinolinoneuntreated groups. Conclusion： The data suggest that 5-Aminoisoquinolinone can inhibit the adhesion of HT-29 cells to human umbilical vein endothelial cells. 5-Aminoisoquinolinone also can inhibit poly （adenosine 5＇-diphosphate ribose） polymerase activation and the expressions of ICAM-1 and P-selectin in HT-29 cells. 5-Aminoisoquinolinone probably contributes to the prevention of tumor cell metastasis. Further study is needed.     

The effect of methamphetamine on serotonin and its metabolite in the suprachiasmatic nucleus: A microdialysis study

Summary The suprachiasmatic nucleus (SCN) has been identified as a major circadian pacemaker. Methamphetamine has been shown to modify the behavior of circadian rhythms. We detected extracellular serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the SCN in freely moving rats, using a microdialysis method, to investigate biochemical effects of methamphetamine in the SCN. Methamphetamine infusion into the SCN dose-dependently increased extracellular 5-HT and decreased extracellular 5-HIAA.     

Interactions between serotonin and substance P in the spinal regulation of nociception

Interactions between 5-hydroxytryptamine (5-HT) and substance P (SP) in the mouse spinal cord were investigated using the tail-flick test and the behavioral response evoked by intrathecal (i.th.) SP or i.th. 5-HT. I.th. injection of 5-HT (20 μg) or the 5-HT₁ receptor agonists(+)-8-hydroxy-2-(di-n-propylamino)tetralin ((+)-8-OH-DPAT) (20 μg) or 5-methoxy-3(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole (RU 24969) (20 μg) markedly inhibited the tail-flick reflex. The effect of these compounds was reduced when SP (5 μg) was given i.th. 55 min, or 55 and 45 min before the agonists. The tail-flick latencies recorded 5 min before injection of a 5-HT agonist were similar in animals treated with SP or vehicle. The changes in the tail-flick test were not due to changes in tail skin temperature since only minimal differences in the skin temperature were recorded between the groups injected with SP or vehicle. I.th. injection of SP (10 ng) or 5-HT (2 μg) produced a similar behavioral response consisting of biting, licking and scratching of the caudal part of the body, indicative of nociceptive stimulation. The responses both to i.th. SP and 5-HT were reduced after i.th. application of SP receptor antagonist [d-Arg¹,d-Trp^7,9,Leu¹¹]-SP (Spantide) (5 μg), as well as 5 min after i.th. injection of the 5-HT receptor antagonist metergoline (4 μg). The data may indicate functional interactions between SP and 5-HT in the mouse spinal cord, which may take place in neurons involved in the processing of nociception.     

Application of median-effect in quantitative analysis of antitumor drugs in vitro

Objective: To analyze quantitatively the synergistic and antagonistic effects of combined oxymatrine (OMT) and 5-fluorouracil (5-GU) on a cell line of human liver cancer (HepG2) with median-effect principle in vitro. Methods: The median-effect principle and MTT method were used in the quantitative analysis of effects of the two drugs. Results: Cytotoxic activity of the individual drugs enhanced as drug concentration increased. As fa=0.41, a CI equal to 1 indicated additivity; fa<0.41, a CI less than 1 indicated synergy; and fa>0.41, a CI greater than 1 indicated antagonism. The sequence of administration did not influence the cytotoxic activity of the combined antitumor drugs. The ratio of drug concentration was a factor that can influence the killing effect. Conclusion: The combined drugs interaction (CI<1) was synergistic at lower concentration and antagonistic at higher concentration. The ratio of drug concentration is a factor that can influence the killing effect. Biography: HE Song(1965–), male, doctor of medicine, associate professor, Chongqing Medical University, majors in gastroenterology.     

Discriminative stimulus properties of the serotonin agonist MK 212

In an attempt to clarify the role of 5-hydroxytryptamine (5-HT) in the discriminative stimulus properties of MK 212 (6-chloro-2[1-piperazinyl]pyrazine), male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg of this compound from saline. While the putative 5-HT agonists fenfluramine and m-chlorophenylpiperazine (MCPP) mimicked MK 212 in a dose-related manner, d-lysergic acid diethylamide (LSD), 8-hydroxy-2(di-n-propylamino)tetralin (8-OHDPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine, Ru 24969, and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) failed to substitute completely. The 5-HT₁/5-HT₂ antagonists BC 105, metergoline, and methysergide completely blocked the MK 212 cue, while the selective 5-HT₂ antagonists ketanserin and pirenperone, the dopamine antagonists haloperidol and spiperone, and the beta-noradrenergic antagonist propranolol were without effect. The substitutions of fenfluramine and MCPP for MK 212 support a role for 5-HT in the MK 212 cue; however, the lack of substitution of many other 5-HT agonists is difficult to explain. The complete antagonism by 5-HT₁/5-HT₂ but not by selective 5-HT₂, antagonists suggests the possibility that 5-HT₁ receptors mediate the stimulus properties of MK 212. Further research is needed to support this hypothesis and to investigate the relative role of 5-HT and other neurotransmitters in the stimulus effects of MK 212.Portions of this research were presented at the Meeting of the Committee on Problems of Drug Dependence Satellite Session (International Study Group Interested in Drugs as Reinforcers and the Society for the Stimulus Properties of Drugs) in Baltimore, MD (1985)     

Dose-dependent headache response and dilatation of limb and extracranial arteries after three doses of 5-isosorbide-mononitrate

Summary The aim of the present study was to compare the ability of different doses of isosorbide-5-mononitrate (5-ISMN) to cause dilatation of medium sized and small arteries, and to examine the intensity and duration of any headache produced. Ten healthy volunteers each received 3 doses of 5-ISMN and placebo on separate days. The diameters of the radial and superficial temporal arteries were repeatedly measured with high frequency ultrasound and pain was scored using a 10 point verbal scale.A clear dose-relationship was found for plasma concentrations and headache, and for changes in the diameter of the temporal artery, but not for the radial artery.It is concluded that headache after 5-ISMN is caused by arterial dilatation or by mechanisms responsible for the arterial dilatation. Ultrasound monitoring of arterial diameters is an important and sensitive tool in the evaluation of nitrates and other vasodilators.