Interaction of some 2-hydroxybenzylpiperidines with dopamine receptors

Some N-alkyl derivatives of 2-(3-hydroxybenzyl)piperidine and of 2-(3,4-dihydroxybezyl)piperidine were synthesized and evaluated pharmacologically in vitro by competition with [3H]spiperone for binding to a homogenized rat striatal tissue, and for ability to stimulate adenylate cyclase. The N-methyl-2-(3,4-dihydroxybenzyl)piperidine shows a fairly good affinity for the D-2 dopamine receptor. The N-alkyl 2-(3,4-dihydroxybenzyl)piperidines produce a faible stimulation of adenylate cyclase activity.     

Feasibility of withholding antibiotics in selected febrile neutropenic cancer patients.

PURPOSE: To investigate the feasibility of withholding antibiotics and early discharge for patients with chemotherapy-induced neutropenia and fever at low risk of bacterial infection by a new risk assessment model. PATIENTS AND METHODS: Outpatients with febrile neutropenia were allocated to one of three groups by a risk assessment model combining objective clinical parameters and plasma interleukin 8 level. Patients with signs of a bacterial infection and/or abnormal vital signs indicating sepsis were considered high risk. Based on their interleukin-8 level, remaining patients were allocated to low or medium risk for bacterial infection. Medium-risk and high-risk patients received standard antibiotic therapy, whereas low-risk patients did not receive antibiotics and were discharged from hospital after 12 hours of a febrile observation. End points were the feasibility of the treatment protocol. RESULTS: Of 196 assessable episodes, 76 (39%) were classified as high risk, 84 (43%) as medium risk, and 36 (18%) as low risk. There were no treatment failures in the low-risk group (95% CI, 0% to 10%). Therefore, sensitivity of our risk assessment model was 100% (95% CI, 90% to 100%), the specificity, positive, and negative predictive values were 21%, 13%, and 100%, respectively. Median duration of hospitalization was 3 days in the low-risk group versus 7 days in the medium- and high-risk groups (P < .0001). The incremental costs of the experimental treatment protocol amounted to a saving of 471 (US $572) for every potentially low-risk patient. CONCLUSION: This risk assessment model appears to identify febrile neutropenic patients at low risk for bacterial infection. Antibiotics can be withheld in well-defined neutropenic patients with fever.     

Indolizine derivativatives with biological activity III: 3-(3-Aminopropyl)-2-methylindolizine, 3-(3-Aminopropyl)-2-methyl-5,6,7,8-tetrahydroindolizine, and their N -alkyl derivatives.

The syntheses and a preliminary pharmacological evaluation of some aminopropylindolizines and aminopropyltetrahydroindolizines are reported. All compounds showed anti-5-hydroxytryptamine, anti-histamine, and antiacetylcholine activities. Some also exhibited weak CNS activity.     

Gas-gangrene following arthroscopic surgery

An arthroscopic anterior cruciate ligament repair was followed by gas-gangrene and the development of a compartment syndrome. Treatment consisted of extensive fasciotomy, debridement, and antibiotic therapy with penicillin G, cefotiam, and metronidazole. The patient was also treated with five sessions of hyperbaric oxygen in a pressure chamber for a duration of 2 h per session. This therapeutic regimen resulted in the preservation of a functionally intact extremity despite severe complication.     

肺部X射线照射后炎性细胞因子在支气管上皮细胞中的表达

目的研究C57BL/6J小鼠双肺照射12Gy后,炎性细胞因子肿瘤坏死因子-α(TNF-α)、白介素-1α(IL-1α)和白介素-6(IL-6)蛋白在肺组织中的表达。方法实验组小鼠给予双肺单次照射12Gy,对照组小鼠在相同条件下双肺假照射0Gy。分别于照射后0·5、1、3、6、12、24、48和72h,1、2、4、8、16和24周处死,通过免疫组织化学方法和图像分析定量检测肺组织中TNF-α、IL-1α和IL-6蛋白的表达。结果胸部照射后数小时,上述炎性因子蛋白表达即比对照组显著增加。在随后的急性放射性肺炎阶段,支气管上皮以及肺间质的炎性细胞产生了大量的TNF-α(最大值出现在全肺照射后第4周,9·74%±1·78%)、IL-1α(最大值出现在全肺照射后第8周,14·76%±7·77%)和IL-6(最大值出现在全肺照射后第8周,4·28%±1·33%)。结论肺部照射以后,在胸部照射的最初数小时以内,支气管上皮是上述炎性因子最重要的来源,这些炎性细胞因子进一步通过征集和激活炎症细胞来促进和放大放射性肺炎的产生和发展。     

Synthesis and dopamine receptor affinities of 2-(4-fluoro-3- hydroxyphenyl)ethylamine and N-substituted derivatives

The synthesis of 2-(4-fluoro-3-hydroxyphenyl)ethylamine (26) and of some N,N-dialkyl derivatives (27-30) starting from 4-fluoro-3-hydroxytoluene and their in vitro binding affinities for dopamine (DA) receptor are reported. The amine 26 can be regarded as a molecular modification of DA in which the para hydroxyl group is replaced by fluorine. The new compounds 26-30 were evaluated for their affinity at D-1 and D-2 DA receptor subtypes by displacement of [3H]SCH 23390 (D-1 selective) and [3H]spiperone (D-2 selective). The amine 26 had about 2-fold less affinity for D-1 and D-2 binding sites than DA. The substitution of the amino group with ethyl, n-propyl, and 2-phenylethyl groups decreased the affinity for D-1 binding sites but greatly enhanced the effectiveness on D-2 binding sites. The N-ethyl- (28) and N-n-propyl-N-(2-phenylethyl)-2-(4-fluoro-3- hydroxyphenyl)ethylamine (30) were the most potent members of the series with high selectivity for D-2 binding sites. A similar effect was observed with isomeric N-n-propyl-N-(2-phenylethyl)-2-(3-fluoro-4-hydroxyphenyl)ethylamine (31) which was approximately 65 times more selective for D-2 sites vs D-1 sites. The introduction of a 2-phenylethyl group on the nitrogen atom induce the highest effect, perhaps as a consequence of an increased liposolubility or of binding to a complementary lipophilic site on the receptor.