Neonatal Binge Ethanol Exposure Using Intubation: Timing and Dose Effects on Place Learning

Neonatal rats were given ethanol using an acute intubation procedure that resulted in daily binge-like exposure with minimal effects on somatic growth. Acquisition of place learning in the Morris water maze was evaluated on postnatal days (PD) 26-31. In Experiment 1, a total of 5.25 g/kg/day of ethanol was administered in two daily intubations on PD 4-6, PD 7-9, or PD 4-9, producing mean peak BACs of 265 mg/dl. Place learning acquisition deficits in a 114-cm-diameter tank were found for the PD 4-9 and PD 7-9 groups, but not the PD 4-6 group. In Experiment 2, either 4.5 or 5.25 g/kg/day of ethanol was administered on PD 7-9 and place learning was tested in a 171-cm-diameter tank. Significant acquisition deficits resulted from the higher dose, and probe trial search patterns for both ethanol groups were significantly less localized than controls. In Experiment 3, no significant effects of either PD 7-9 dose were found on a visible platform task. These findings reveal selective place learning deficits in this intubation model of neonatal binge exposure, and confirm a temporal window of vulnerability to spatial learning deficits during the second neonatal week.     

庆大霉素负荷量法治疗儿童感染性腹泻240例

目的 :观察庆大霉素负荷量法治疗儿童感染性腹泻的疗效及对肾、耳的毒性。方法 :治疗组 2 40例采用庆大霉素 4mg (kg·d) ,qd ,负荷量给药方案 ,对照组 190例采用 4mg (kg·d) ,分 3次给药方案。结果 :治疗组、对照组总有效率分别为 90 .0 % ,71.0 % ,差异极显著 ( P <0 .0 1) ,治疗组、对照组肾、耳毒性发生率分别为 1.3 % ,4.4% ,差异显著 ( P <0 .0 5 )。结论 :庆大霉素负荷量治疗方案优于每日 3次给药方案 ,且肾、耳毒性较小。     

盐酸氨溴索雾化吸人辅助治疗新生儿肺炎临床观察

目的:探讨盐酸氨溴索雾化吸入辅助治疗新生儿肺炎的疗效.方法:将60例新生儿肺炎患儿随机分为两组各30例,对照组采用常规抗感染、吸氧、吸痰等治疗,治疗组在对照组常规治疗基础上给予氨溴索30 mg电动压缩雾化吸入,2～3次/d.结果:治疗组总有效率90.0％,明显优于对照组的63.3％(P＜0.01),治疗组血气分析恢复正常时间为(3.50±1.29)d、肺部啰音消失时间(6.23±2.31)d、住院天数(9.51±3.23)d,均较对照组的(6.12±2.35)d、(9.15±3.14)d、(11.00±4.67)d明显缩短,两组比较差异均有统计学意义(P＜0.01).结论:盐酸氨溴索雾化吸入辅助治疗新生儿肺炎具有良好疗效和安全性.     

高剂量表阿霉素在肿瘤患者中的药物动力学和药效学研究

目的：研究高剂量表阿霉素在肿瘤化疗患者体内的药物动力学过程,并初步探讨药效学特点。方法：１１例肿瘤患者接受了包含 １００ｍｇ·ｍ~（－２）高剂量表阿霉素的联合化疗, ＨＰＬＣ法测定血药浓度; ＰＣＮＯＮＬＩＮ程序进行药物动力学房室模型数据拟合和参数计算;血液学毒性指标作为药效学参数,进行药物动力学和药效学相关性及剂量调整因素的研究。结果：高剂量表阿霉素的消除具有典型的三室特征,患者对表阿霉素的代谢存在较大的个体差异;药效学和药物动力学参数之间未见到明显相关性,年龄与血浆清除率之间呈负相关。结论：与低剂量表阿霉素比较,未发现药物动力学参数的差异;年龄是影响清除率的一个重要因素,对高龄患者应适当减少药物剂量;应用１００ｍｇ·ｍ~（－２）表阿霉素患者的耐受性良好。     

Model-Based Adaptive Optimal Design (MBAOD) Improves Combination Dose Finding Designs: an Example in Oncology

Design of phase 1 combination therapy trials is complex compared to single therapy trials. In this work, model-based adaptive optimal design (MBAOD) was exemplified and evaluated for a combination of paclitaxel and a hypothetical new compound in a phase 1 study to determine the best dosing regimen for a phase 2 trial. Neutropenia was assumed as the main toxicity and the dose optimization process targeted a 33% probability of grade 4 neutropenia and maximal efficacy (based on preclinical studies) by changing the dose amount of both drugs and the dosing schedule for the new drug. Different starting conditions (e.g., initial dose), search paths (e.g., maximal change in dose intensity per step), and stopping criteria (e.g., “3?+?3 rule”) were explored. The MBAOD approach was successfully implemented allowing the possibility of flexible designs with the modification of doses and dosing schedule throughout the trial. The 3?+?3 rule was shown to be highly conservative (selection of a dosing regimen with at least 90% of the possible maximal efficacy in less than 21% of the cases) but also safer (selection of a toxic design in less than 2% of the cases). Without the 3?+?3 rule, better performance was observed (>67% of selected designs were associated with at least 90% of possible maximal efficacy) while the proportion of DLTs per trial was similar. Overall, MBAOD is a promising tool in the context of dose finding studies of combination treatments and was showed to be flexible enough to be associated with requirements imposed by clinical protocols.     

Pharmacodynamics of in Vivo Nitroglycerin Tolerance in Normal Conscious Rats: Effects of Dose and Dosing Protocol

PURPOSE: We examined the effects of dose and dosing protocol on the pharmacodynamics of in vivo nitroglycerin (NTG) tolerance in conscious rats. Mechanism-based pharmcokinetic/pharmacodynamic (PK/PD) models were tested for their ability to describe the observed data. METHODS: Rats were infused with 1, 3, or 10 microg/min of NTG or vehicle for 10 h. Peak mean arterial pressure (MAP) response to an hourly 30 microg i.v. NTG challenge dose (CD) was measured before, during, and at 12 and 24 h after infusion. In separate experiments, the MAP effects of repeated bolus doses of NTG were compared to those after a continuous infusion, both at a total dose of 510 microg NTG. RESULTS: NTG tolerance was indicated by a decrease in peak MAP response to the CD, relative to the preinfusion peak MAP response. Tolerance toward the MAP effects of bolus CD was observed within 1 h of 10 microg/min of NTG infusion (26.8 +/- 2.8% vs. 10.6 +/- 0.4% for 0 and 1 h, respectively, p < 0.001), and the rate and extent of tolerance development increased with the infusion dose. No apparent MAP tolerance was observed when NTG was given as multiple bolus doses whereas significant MAP tolerance was observed when this dose was infused continuously. PK/PD modeling indicated that a cofactor/enzyme depletion mechanism could adequately describe the composite data. CONCLUSIONS: Our data showed that in vivo nitrate tolerance was dose- and dosing protocol-dependent. The pharmacodynamics of tolerance development are consistent with depletion of either critical enzymes or cofactors that are necessary to induce vasodilation.     

Biphasic Dose Response in Low Level Light Therapy

The use of low levels of visible or near infrared light for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing cell death and tissue damage has been known for over forty years since the invention of lasers. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial in mainstream medicine. The biochemical mechanisms underlying the positive effects are incompletely understood, and the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength, fluence, power density, pulse structure and treatment timing has led to the publication of a number of negative studies as well as many positive ones. A biphasic dose response has been frequently observed where low levels of light have a much better effect on stimulating and repairing tissues than higher levels of light. The so-called Arndt-Schulz curve is frequently used to describe this biphasic dose response. This review will cover the molecular and cellular mechanisms in LLLT, and describe some of our recent results in vitro and in vivo that provide scientific explanations for this biphasic dose response.     

低剂量螺旋CT在新生儿头颅扫描中的临床应用

目的评估新生儿低剂量头颅CT扫描的图像质量和临床应用价值。方法对临床怀疑颅脑病变需行CT检查的新生儿80例随机等分成2组,分别行常规剂量和低剂量CT扫描,常规剂量组管电流为180mAs,低剂量组为60mAs,其余参数为管电压120kV,1.5秒/360度,层厚、层间距7mm,轴位扫描,1X3幅图像。记录各组的CT吸收剂量指数(CTDIw);由3位医师采用盲法评判两组扫描剂量的图像质量。结果常规组的CTDIw为45.8mGy,60mA组的CTDIw为9.6mGy,低剂量扫描组的CT吸收剂量指数(CTDIw)仅相当于常规剂量的21.0%,所用图像基本都满足了临床需要。结论螺旋CT应用降低管电流的方法在新生儿头颅扫描时可明显降低射线剂量,并可获得满足临床诊断的图像质量。     

小剂量换血法治疗新生儿红细胞增多症

目的观察小剂量换血生理盐水稀释法治疗新生儿红细胞增多症疗效。方法对150例新生儿红细胞增多症患儿采用每次放血5～10ml,同时由外周静脉输入生理盐水5～20m1．结果小剂量换血治疗1～2次后总治愈率为96．67％．结论小剂量换血生理盐水稀释法疗效好,经济,安全,适于推广应用。     

新生儿肝炎综合征外科治疗的分析

目的对内科保守治疗效果差的8例新生儿肝炎综合征患儿进行手术治疗。方法接受手术日龄为45~75d,术中7例确诊为肝外胆道闭锁,行肝门肠吻合术（kasai手术）1例患儿术中确诊为胆汁浓缩综合征,给予胆道冲洗。结果经随访8例患儿短期疗效满意,黄疸消退,血清胆红素明显下降,大便颜色正常,3例曾出现术后胆管炎,经抗炎及抗感染治疗后好转。结论对内科治疗效果不佳、各项检查提示胆道闭锁的患儿早期应进行手术治疗,kasai手术是治疗胆道闭锁的有效术式。长期疗效尚需进一步观察。     

静滴大剂量氨甲蝶呤／醛氢叶酸治疗血液肿瘤的血药浓度及药效学

目的：本文对不同时间静滴大剂量氨甲蝶呤／醛氢叶酸解救治疗血液肿瘤患者的血药浓度进行监测及药效和毒性反应进行研究。方法：采用高效液相色谱法测定氨甲蝶呤的血药浓度,按不同时间静滴大剂量氨甲蝶呤将４１例病人分为两组;Ｓ组氨甲蝶呤于６ｈ滴完,Ｌ组于１２ｈ滴完,两组均在滴注完６ｈ开始醛氢叶酸救援。在滴注毕０．８、６、４２ｈ采血测定氨甲蝶呤血药浓度。结果：Ｓ组药物浓度在０．０８ｈ显著高于Ｌ组（Ｐ＜０．０１）,６、１８、４２ｈ两组血药浓度无差异（Ｐ＞０．０１）。完全缓解率中位持续完全缓解及中位生存期两组间无显著差异（Ｐ＞０．０５）,Ｌ组毒性反应明显比Ｓ组严重。结论：６ｈ滴完组的疗效比１２ｈ滴完组的好。     

早期小剂量多巴胺治疗新生儿重度窒息的临床效果

目的探讨早期小剂量多巴胺对新生儿重度窒息的治疗效果,以供参考。方法选择2009年4月至2013年3月我院新生儿重度窒息患儿76例为本次研究对象,根据随机法将76例重度窒息患儿随即分为两组,分别为A组患儿38例,B组患儿38例,两组均接受对症综合治疗,B组患者在此治疗基础上于窒息复苏后2h开始应用多巴胺治疗。对比两组患儿临床疗效的差异性。结果对比两组患儿治疗后脏器功能损害发生率发现,B组均明显低于A组,差异具有统计学意义（P〈0．05）。结论早期小剂量多巴胺在新生儿重度窒息的治疗中可明显改善脏器损伤,疗效具有一定的优越性,值得在今后的临床工作中予以推广应用。     

Withdrawal after Narcotic Therapy: A Survey of Neonatal and Pediatric Clinicians

Pharmacists at the 1995 American College of Clinical Pharmacy Pediatric Practice and Research Network meeting volunteered to act as coordinators at their sites and survey pediatric and neonatal nurses, pharmacists, and physicians regarding dependency in neonatal and pediatric patients after therapeutic administration of narcotics. Thirteen (60%) of 21 coordinators returned 244 surveys. Primary symptoms of withdrawal reported by clinicians were agitation (100%), irritability (100%), inconsolability (100%), crying (99%), tremors (98%), high heart rate (98%), fidgets (98%), high blood pressure (97%), less sleep (96%), and sweating (94%). Most clinicians considered narcotic withdrawal to be a problem (74%) that should be treated (87%). A dependency scale is being developed and will include symptoms reported by more than 75% of respondents.     

不同剂量与给药时机口服普萘洛尔在婴幼儿血管瘤中的应用价值

目的:探讨不同剂量与给药时机口服普萘洛尔在婴幼儿血管瘤中的应用价值。方法:选取2017年1月至2018年6月湖北省荆州市中心医院收治的96例血管瘤患儿,按随机数表法为A组和B组各48例。两组患儿均采用“阶梯式”治疗方法,A组最终维持剂量1.0 mg/(kg·d),B组最终维持剂量2.0 mg/(kg·d),比较两组患儿达到停药终点时的总体疗效、达到显效和临床治愈时间及持续治疗时间。依据开始治疗年龄将两组患儿各分为>3个月和≤3个月两个亚组,比较上述指标的差异。记录不良反应发生率和复发率。结果:达到停药终点时,A组和B组临床治愈率比较差异无统计学意义(P>0.05)。临床治愈患儿中,B组达到显效和临床治愈时间短于A组(P<0.05)。A组持续治疗时间长于B组(P<0.05)。达到停药终点时,≤3个月组临床治愈率高于>3个月组,但差异无统计学意义(P>0.05)。临床治愈患儿中,≤3个月组达到显效和临床治愈时间短于>3个月组(P<0.05)。≤3个月组持续治疗时间短于>3个月组(P<0.05)。两组患儿不良反应及复发率比较差异无统...     

Gentamicin Nephrotoxicity in Rat: Some Biochemical Correlates

Abstract: The present work examines the effect of treatment of rats with graded doses of the aminoglycoside antibiotic gentamicin on the concentration of reduced glutathione (GSH) and diamine oxidase (DAO) activity in the kidney, and DAO activity, creatinine and magnesium (Mg) in the plasma. The animals were given the antibiotic intramuscularly in doses of 20, 40, and 80 mg/kg/day for 6 days, and were killed 24 hr after the last injection. In another experiment rats were injected intramuscularly with gentamicin at a dose of 80 mg/kg/day for 6 days and were killed 1, 7 or 14 days after the last injection, and the above parameters were measured. Gentamicin reduced the body weights of rats in a dose-dependent manner. The weight reductions were most marked on days 4, 5 and 6 of the treatment. The body weights gradually recovered on withdrawing of the drug, and by day 14, they were not significantly different from those of the controls. Gentamicin produced significant and dose-dependent decreases in the renal concentration of GSH. Seven and 14 days after withdrawing the drug, the GSH concentrations were still significantly below that of the controls. Plasma Mg concentrations were significantly decreased, and plasma creatinine concentrations significantly increased by gentamicin. These effects persisted 7 and 14 days after cessation of treatment. Plasma DAO activity was not detectable in the control or gentamicin-treated rats. In the renal cortex, the activity of the enzyme, measured 1, 7 and 14 days after the treatment, was not significantly different from that of the control. Histopathologically, the drug produced dose-dependent proximal renal tubular necrosis. Seven days after withdrawal of gentamicin, the degree of necrosis was less marked, and 14 days after drug withdrawal, renal histology was apparently normal.