Reduction in Internal Carotid Arterial Blood Flow Velocity in Children During Antiepileptic Drug Therapy with Clinical Dosages

Summary: We studied the effect of antiepileptic drugs (AEDs) on internal carotid artery (ICA) blood flow velocity, as an index of total cerebral blood flow (CBF). The subjects were 45 newly diagnosed children with febrile convulsion or epilepsy who were seizure-free for a period long enough not to affect the results. They had no neurologic deficit, received fixed monotherapy, and were examined by a noninvasive Doppler ultrasound method, in comparisonwith 13 age-matched normal volunteers with no AED. In 30 patients, the measurements were performed before and after AED administration [10 with phenobarbital (PB), 10 with carbamazepine (CBZ), and 10 with valproate (VPA)], and performed before and after AED discontinuation in the remaining 15 patients (all with PB). Normal volunteers underwent the two consecutive examinations with a mean interval equal to that of the entire patient group, and there was no difference in velocity values between the measurements. In patients receiving CBZ or VPA, a significant reduction was noted in blood flow velocity after drug administration. Although velocity values in the patients receiving PB did not change after drug administration, they were significantly increased after complete discontinuation. In the present study, a slight but significant reduction in CBF caused by AED administration at therapeutic doses in children was suggested.     

Short-term niflumic-acid-induced acute renal failure in children

Several reports emphasize the adverse effects of non-steroidalanti-inflammatory drugs (NSAIDs) on renal function. We haveobserved over the last 10 years seven cases of acute renal failure(ARF) due to immune interstitial nephritis in children. A recommendedoral or rectal dose of niflumic acid was prescribed for ear-nose-throatdisorders, Length of exposure was 1–5 days. Clinical symptoms (oedema, oliguria or anuria) appeared between3 and 6 days. Three patients had previously received the drug.Hypersensitivity signs (fever, skin rash, eosinophilia, and/orincreased IgE) were present in all cases, leukocyturia in fivecases, and haematuria in six cases. Renal biopsy showed interstitiallesions with lymphocyte, eosinophil, and plasma cell infiltrateswithout tubular cell necrosis. Glomeruli were normal on light-microscopy,except in one patient. Electron-microscopy showed extensivepodocyte fusion in two patients, who had clinical and laboratoryevidence of nephrotic syndrome (NS). ARF rapidly disappeared after NSAID withdrawal, except in twopatients whose renal failure was irreversible despite methylprednisolonebolus. ARF is very rare in children treated with niflumic acid.When ARF occurs, different pathophysiological mechanisms areinvolved but the most common is immunological.     

头孢替唑钠与头孢哌酮治疗小儿急性细菌性下呼吸道感染的临床疗效比较

目的:评价头孢替唑钠治疗小儿急性细菌性下呼吸道感染的临床有效性、安全性。方法:轻、中度急性细菌性下呼吸道感染患儿115例分成2组,头孢替唑组58例,予头孢替唑钠20～80mg/(kg·d),溶于10%葡萄糖溶液中,分2次静脉滴注。头孢哌酮组57例,予头孢哌酮50～150mg/(kg·d),分二次静脉滴注。两组均以7~10d为一疗程。结果:头孢替唑钠组与头孢哌酮组的临床有效率分别为93%与91%(P>0.05),细菌清除率分别为92%与89%(P>0.05)。两组均无明显的不良反应。结论:头孢替唑可作为治疗小儿轻、中度急性细菌性下呼吸道感染有效和安全的抗生素。     

一种新型人TNFα对人肝癌裸鼠移植瘤的抗瘤作用

用人肝癌Ｂｅｌ７４０２瘤株建立了人肝癌裸鼠移植瘤模型，探讨新型重组人ＴＮＦａ对这种移植瘤的抗瘤作用，结果表明，ｒｈＴＦａＤ１１ａ和原型重组人ＴＮＦａ的抑瘤率在３０％左右时，后者后用的活性产闰数是前者的２倍；两者用量相同时，前者的抑产经比后者提高２３个百分     

改进虎杖、鸡血藤炮制方法的研究

对虎杖、鸡血藤作了切制、干燥时间和成品、主要成分及水浸出物的比较。结果表明,趁鲜切片优于传统切块、再切片,既能提高饮片的规格质量和成分含量,亦能减少重复劳动,节约能源,避免药材的浪费。     

几种咪唑类外用抗真菌药接触性皮炎的初步研究

用３种常用外用咪唑类抗真菌药，达克宁霜（咪康唑）、联苯苄唑霜及癣敌软膏（益康唑）对１８５例有外用此类药物史的皮肤病病人进行了斑贴试验。结果斑试刺激反应及过敏反应阳性率分别为３．８％及４．３％，说明此类药物是常见的致敏原及刺激原之一。抗真菌剂致敏可出现急性接触性皮炎，应与真菌病加重相鉴别。斑贴试验可以诊断抗真菌剂接触性皮炎，并区分刺激反应与过敏反应。     

Comparison of the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers

Background : Nonsteroidal anti–inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis which may result in impaired platelet function. Because NSAIDs have different abilities to inhibit cyclo–oxygenases we compared the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers. Methods : Ten healthy male volunteers were given ketoprofen 1.4 mg kg^-1, ketorolac 0.4 mg kg^-1 and diclofenac 1.1 mg kg^-1 in saline i.v. on three different occasions, at more than one–week intervals, in a randomized double–blind crossover study. Platelet function was evaluated before (sample 0), 2 (sample 2) and 24 h (sample 3) after the beginning of the infusion. Results : Two of the volunteers had no secondary platelet aggregation in their aggregation curves before the experiment (sample 0, studied three times) and their results were excluded from the final analysis. Diclofenac inhibited adrenaline (0.9 μg–ml^-1) induced platelet aggregation less (median maximal aggregation 22.5%) than ketoprofen (18.3%) and ketorolac (15.7%) (P<0.05) in sample 2. In the ketorolac group in sample 3 an impairment of adrenaline (0.9 ng ml^-1) induced platelet aggregation was still seen (26.7%) (P<0.05) but not in the other groups. Diclofenac did not affect adenosine diphosphate (ADP) induced platelet aggregation. However, ketorolac caused an impairment in ADP (3 μM and 6 μM) induced platelet aggregation and ketoprofen in ADP (6 μM) induced platelet aggregation in sample 2. Bleeding time was prolonged (P<0.05) after ketoprofen and ketorolac (sample 2) but not after diclofenac. Platelet retention on glass beads was unaffected by the tested drugs. Conclusion : Ketoprofen, ketorolac and diclofenac caused a reversible platelet dysfunction. Diclofenac had the mildest effect, while platelet dysfunction was still seen 24 h after the beginning of ketorolac.     

Loading anticancer drugs into HDL as well as LDL has little affect on properties of complexes and enhances cytotoxicity to human carcinoma cells

Low density lipoprotein (LDL) has been found to represent a suitable carrier for cytotoxic drugs that may target them to cancer. This study investigated whether very low density lipoprotein (VLDL), LDL and high density lipoprotein (HDL) can be used to effectively incorporate four cytotoxic drugs, 5-fluorouracil (5-FU), 5-iododeoxyuridine (IUdR), doxorubicin (Dox) and vindesine; characterized the complexes; and examined the effect of incorporation on drug cytotoxicity against HeLa cervical and MCF-7 breast carcinoma cells. Significant drug loading was achieved into all three classes of lipoproteins, consistent with the sizes and hydrophobicity of the drugs. The relative loading efficiency was found to be vindesine>IUdR>Dox>5-FU for all three classes of lipoproteins. As shown by electron microscopy (EM), drug incorporation did not affect the size or morphology of the lipoproteins. Differential scanning calorimetry (DSC) showed that drug loading did not significantly change the thermal transition temperature of core lipids in the lipoproteins. The transition enthalpy was changed only for LDL–Dox and LDL–vindesine. The drugs remained stable in the lipoproteins as determined by high performance liquid chromatography (HPLC). EM, DSC and HPLC data suggest that drugs were incorporated into lipoproteins without disrupting their integrity and drugs remained in their stable forms inside lipoproteins. Compared with free drugs in cytotoxicity assays, the IC₅₀ values of LDL– and HDL–drug complexes were significantly lower (2.4- to 8.6-fold for LDL complexes and 2.5- to 23-fold for HDL complexes). All free or lipoprotein-bound drug formulations were comparably more cytotoxic against MCF-7 than HeLa cells. Upregulating the lipoprotein receptors enhanced, and downregulating them inhibited, the cytotoxicity, indicating the mechanistic involvement of lipoprotein receptor pathways. Complexes of all four drugs with VLDL, in contrast to LDL and HDL, had the same cytotoxicity as the four corresponding free drugs. Our results suggest that further studies are required of the potential of HDL to be a cancer targeting drug carrier.     

Treatment of Status Epilepticus in Adults: Guidelines of the Italian League Against Epilepsy

Summary:  Status epilepticus (SE) is a medical emergency which can lead to significant morbidity and mortality and requires prompt diagnosis and treatment. SE is differentiated into generalized or partial SE on the basis of its electro-clinical manifestations. The guidelines for the management of SE produced by the Italian League against Epilepsy also distinguish three different stages of SE (initial, established and refractory), based on time elapsed since the onset of the condition and responsiveness to previously administered drugs. Treatment should be started as soon as possible, particularly in generalized convulsive SE, and should include general support measures, drugs to suppress epileptic activity and, whenever possible, treatments aimed at relieving the underlying (causative) condition. Benzodiazepines are the first line antiepileptic agents, and i.v. lorazepam is generally preferred because it is associated with a lower risk of early relapses. If benzodiazepines fail to control seizures, i.v. phenytoin is usually indicated, though i.v. phenobarbital or i.v. valproate may also be considered. Refractory SE requires admission to an intensive care unit (ICU) to allow adequate monitoring and support of respiratory, metabolic and hemodynamic functions and cerebral electrical activity. In refractory SE, general anesthesia may be required. Propofol and thiopental represent first line agents in this setting, after careful assessment of potential risks and benefits.