Canine laryngeal transplantation: preliminary studies and a new heterotopic allotransplantation model

While transplantation of the larynx may eventually be useful in post-laryngectomy reconstruction, three criteria must first be met before human transplants can be attempted: transplant viability must be high, immunosuppression must be safe and effective and functional recovery of the larynx must occur. To study these first two criteria, a total of 11 canine larynx transplants were performed: 3 autografts, 6 orthotopic allografts and 2 heterotopic allografts. The rationale and technical performance of these different transplant procedures are reviewed in detail. Orthotopic transplant recipients received cyclosporin A (CsA) while the heterotopic allograft recipients received RS-61443 and methylprednisolone in addition to CsA. Overall, 9 of 11 of the transplants remained viable. In contrast, all 3 autografted animals developed esophageal-cutaneous fistulas; 2 developed sepsis and were sacrificed on post-operative days (POD) 5 and 28, respectively. The third survived for 91 days and demonstrated a high degree of regeneration in the recurrent and superior laryngeal nerves of the transplant. Orthotopically transplanted dogs also had a high morbidity and perioperative mortality (5 of 6 animals). The single long-term survivor was treated with CsA alone, but developed complete transplant rejection on POD 33. The two heterotopic transplant recipients had no perioperative morbidity and the combination of CsA, RS-61443 and methylprednisolone given these latter animals was effective in the longterm prevention of rejection. One of these heterotopic recipients died of sepsis on POD 68 while the other remained alive and well on POD 168. Our present findings show that currently available microsurgical techniques allow experimental canine laryngeal transplantation to be done with significantly high transplant viability rates. In the dog, CsA alone is inadequate for the long-term prevention of transplant rejection while combined therapy with CsA, RS-61443 and methylprednisolone can provide long-term rejection-free larynx transplant survival. The newly developed heterotopic larynx transplant model allows studies of transplant viability, rejection mechanisms and neural regeneration and functional recovery to be performed with minimal animal morbidity and lowered research costs.Presented at the combined meeting of the Society of Head and Neck Surgeons and the European Organization for Research and Treatment of Cancer (EORTC), Paris, France, 25–28 May, 1994     

Cardiac effects of contrast media in MR angiography: evaluation in an experimental model of myocardial ischemia

RATIONALE AND OBJECTIVES: The authors evaluated the cardiac tolerability of paramagnetic contrast agents for magnetic resonance (MR) angiography in an in vitro model of ischemic rat heart. MATERIALS AND METHODS: The left anterior descending coronary artery was temporarily occluded in a perfused rat heart model to induce cardiac ischemia and reperfusion. A dose of 0.4 mL of gadobenate dimeglumine, of gadopentetate dimeglumine, or of D-mannitol was injected directly into the aorta both during the ischemia and during the reperfusion period. The left ventricular pressure and heart rate were recorded. RESULTS: Myocardial ischemia resulted in decreased cardiac activity, with a reduction in left ventricular pressure and heart rate. A further decrease in cardiac activity was temporarily induced by injection of contrast medium during both the ischemic and early reperfusion phases. Less marked responses were induced by a hyperosmolal solution of mannitol. CONCLUSION: These results suggest that the transient cardiac effects induced by bolus injection of paramagnetic contrast medium may be regarded as the combined effects of the osmotoxicity of the contrast medium solution and the chemotoxicity of the contrast medium molecule.     

Cytotoxic constituents from the roots ofAnthriscus sylvestris

Activity-guided fractionation of the roots of Anthriscus sylvestris resulted in the isolation and characterization of five cytotoxic compounds, deoxypodophyllotoxin (1), falcarindiol (2), and angeloyl podophyllotoxin (5) from the hexane soluble fraction and morelensin (3), bursehernin (4) from the chloroform soluble fraction. It is the first report of the occurrence of compound 5 in nature.     

THIP inhibits feeding behavior in fasted rats

The effects of 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol (THIP) were compared with those of d-amphetamine and GABA in fasted rats. Intravenously-administered THIP produced a dose-dependent decrease in food consumption (ED₅₀1.5 mg/kg) by an action that was not reversed by prior subcutaneous or simultaneous intravenous (IV) injection of bicuculline. d-Amphetamine-SO₄ also produced a decrease in food consumption in this model (ED₅₀0.2 mg/kg, IV). Unlike THIP, GABA (in doses up to 100 mg/kg, IV) did not produce a marked anorexigenic effect. These results provide further evidence that THIP can penetrate the blood-brain barrier, and that central GABA-ergic systems are involved in controlling food intake.     

氧氟沙星加双黄连注射液静脉滴注致肝损害1例

氧氟沙星 (ｏｆｌｏｘａｃｉｎ)和双黄连 (Ｓｈｕａｎｇｈｕａｎｇｌｉ ａｎ)已成为临床常用的抗菌药 ,但其不良反应亦不可忽视。我们曾遇见 1例用该 2药治疗上呼吸道感染引起严重肝功能损害 ,报道如下。病人男性 ,2 1ａ。主要因咽痛、咯痰、发热 2ｄ入院。病人于入院前 2ｄ出现咽痛、咯黄痰、胸痛、发热 (Ｔ38.9℃ )。诊断为上呼吸道感染。在当地卫生所给予氧氟沙星注射液(四川科伦大药厂生产 ,规格 :1 0 0ｍＬ :0 .2ｇ批号 0 1 30 1 2 )0 .2ｇ(1 0 0ｍＬ) +双黄连注射液 (齐齐哈尔第二制药厂生产 ,规格 :每支 2 0ｍＬ批号 30 0 1 32 ) 2 0…     

1999至2001年广州地区临床常见肠杆菌科细菌耐药性监测结果分析

目的 了解临床分离常见肠杆菌科细菌的耐药性。方法 统一采用纸片扩散法进行实验，以美国NCCLS文件为判断标准，每次监测均有质控数据。结果 共有11家广州市三级甲等医院实验室参加耐药性监测，三年共统计临床常见肠杆菌科细菌3147株。结论 对肠杆菌科细菌，亚胺培南的耐药率最低，可考虑为临床首选药物，阿米卡星、头孢他啶耐药率相对较低，可选择用药。庆大霉素的耐药率有逐年下降的趋势，将来可能成为临床一线药。而磺胺甲噁唑／甲氧苄啶、四环素、萘啶酸等耐药率相对较高，应慎用。氨节西林的耐药率很高，应避免使用。     

京、沪、穗三城市2001年—2002年抗病毒药物利用分析

目的 :通过京、沪、穗抗病毒用药的药物利用分析 ,为药品研究、生产、流通和宏观控制提供参考。方法 :利用《全国医药信息网》提供的京、沪、穗三地的抗病毒药品 2 0 0 1年和 2 0 0 2年的统计数据 ,通过药品消耗排序、趋势分析、DDDs等指标 ,分析抗病毒药品的利用情况和市场走势。结果 :抗病毒药品的消耗总体呈增长趋势 ,其中专利品种如拉米夫定的优势远远大于仿制品种 ;国产药品目前在抗病毒药品消耗总金额中占绝对优势 ;京、沪、穗抗病毒用药金额差别较大 ,以广州最高。结论 :抗病毒药品具有广阔的市场前景 ,但要重视低水平的重复仿制与科技创新的矛盾。具有自主知识产权的专利品种是保持市场竞争力的关键。     

国产班布罗的平喘作用

目的　研究国产班布特罗的平喘作用。方法　采用豚鼠整体引喘法及兔肺溢流法。结果　班布特罗 (ig ,1 4、2 8、5 6mg·kg-1)同间羟叔丁肾上腺素作用相似 ,均具有平喘及松驰气管平滑肌的作用。结论　国产班布特罗具有明显的平喘作用     

去甲氧柔红霉素联合方案治疗难治性急性淋巴细胞白血病的远期疗效

目的探讨应用去甲氧柔红霉素（ＩＤ）为主的联合化疗方案治疗难治性儿童急性淋巴细胞白血病（ＡＬＬ）的远期疗效及其临床应用价值。方法初治诱导缓解方案用ＶＩＬＰ（长春新碱、去甲氧柔红霉素、左旋门冬酰胺酶、泼尼松）。完全缓解（ＣＲ）后作巩固治疗及庇护所治疗，然后再用ＶＩＬＰ作早期强化治疗。复发者诱导治疗用ＩＡ（去甲氧柔红霉素、阿糖胞苷）方案。ＣＲ后巩固和早期强化治疗用初治者同样方案。结果１０例初治患儿９例获ＣＲ，７例复治患儿５例获ＣＲ，总ＣＲ率为８２％（１４／１７）。ＣＲ的１４例中持续ＣＲ（ＣＣＲ）＞３年者４例，＞２年者４例，＞１年者１例。结论用去甲氧柔红霉素为主的联合方案是治疗难治性儿童ＡＬＬ有效的方法，对初治患儿作为一线药物其远期疗效会更好。     

Effects of vecuronium and rocuronium in antagonistic laryngeal muscles and the anterior tibial muscle in the cat

BACKGROUND: Adequate vocal cord paralysis and full recovery of laryngeal muscle function are important when muscle relaxants are used perioperatively. This study was designed to compare the effects of vecuronium and rocuronium at the vocal cord abductor and adductor muscles and the anterior tibial muscle in cats. METHODS: Twelve adult cats were studied under pentobarbitone-N2O/O2-anesthesia. After supramaximal electrical stimulation of the peroneal nerve and the recurrent laryngeal nerve (0.1 Hz and intermittent train-of-four) evoked electromyographic responses were obtained from the anterior tibial muscle, the posterior cricoarytenoid muscle (vocal cord abductor) and two vocal cord adductor muscles, the lateral cricoarytenoid and the vocal muscle. Six cats received bolus doses of increasing size of vecuronium (ED90 22.5 microg x kg(-1)) and six cats rocuronium (ED90 90 microg x kg(-1)). RESULTS: Equipotent doses of vecuronium and rocuronium caused a similar degree of paralysis in all muscles (vecuronium ED90: 70% blockade at the posterior cricoarytenoid, 83% at the lateral cricoarytenoid, 84% at the vocal muscle and 90% at the anterior tibial muscle; rocuronium ED90: 71% at the posterior cricoarytenoid, 67% at the lateral cricoarytenoid, 78% at the vocal muscle and 90% at the anterior tibial muscle; vecuronium 2 x ED90: 93% blockade at the posterior cricoarytenoid, 95% at the lateral cricoarytenoid, 97% at the vocal muscle and 99% at the anterior tibial muscle; rocuronium 2 x ED90: 89% blockade at the posterior and lateral cricoarytenoid, 93% at the vocal muscle and 100% at the anterior tibial muscle). Onset time was significantly shorter at the posterior cricoarytenoid muscle (290 s) compared to the lateral cricoarytenoid muscle (400 s) after vecuronium ED90 and to the vocal muscle (150 s versus 210 s) after rocuronium ED90. Compared to the anterior tibial muscle (interval 25-75%: 6.5 min after vecuronium 2 x ED90 and 3.3 min after rocuronium 2 x ED90 and to the posterior cricoarytenoid muscle (interval 25-75%: 7 min after vecuronium 2 x ED90 and 4.3 min after rocuronium 2 x ED90), recovery of laryngeal adductor muscle function was markedly delayed with both neuromuscular blocking drugs (interval 25-75% at the lateral cricoarytenoid and vocal muscle: 14 min and 15.8 min after vecuronium 2 x ED90 and 10.3 min and 11.6 min after rocuronium 2 x ED90 respectively). CONCLUSION: In cats, the time course of neuromuscular blockade after vecuronium and rocuronium differs in antagonistic laryngeal muscles. The protective laryngeal function of glottis closure recovers later than vocal cord abduction after both vecuronium and rocuronium.