Single Daily Dose Methimazole Treatment of Hyperthyroidism

The effectiveness of methimazole used in a single daily dose was studied in 47 patients during their initial episode of hyperthyroidism, and in an additional eight patients during a relapse of hyperthyroidism. All patients become euthyroid using this method. Mean time required to achieve a euthyroid state was 16.7±1.1 weeks in the former group, and 14.9±2.9 weeks in the latter. In one patient there was an initial response to single daily dose therapy, but subsequently split dosage was required for control. The single daily dose regimen of antithyroid drugs will control hyperthyroidism in most patients. We have found that propylthiouracil will achieve this more rapidly than methimazole.     

Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study

Miltefosine (MFS) is an alkylphosphocholine used for the local treatment of cutaneous metastases of breast cancer and oral therapy of visceral leishmaniasis. Recently, the drug was reported in in vitro and preclinical studies to exert significant activity against different developmental stages of schistosomiasis mansoni, a widespread chronic neglected tropical disease (NTD). This justified MFS repurposing as a potential antischistosomal drug. However, five consecutive daily 20 mg/kg doses were needed for the treatment of schistosomiasis mansoni in mice. The present study aims at enhancing MFS efficacy to allow for a single 20mg/kg oral dose therapy using a nanotechnological approach based on lipid nanocapsules (LNCs) as oral nanovectors. MFS was incorporated in LNCs both as membrane-active structural alkylphospholipid component and active antischistosomal agent. MFS-LNC formulations showed high entrapment efficiency (EE%), good colloidal properties, sustained release pattern and physical stability. Further, LNCs generally decreased MFS-induced erythrocyte hemolytic activity used as surrogate indicator of membrane activity. While MFS-free LNCs exerted no antischistosomal effect, statistically significant enhancement was observed with all MFS-LNC formulations. A maximum effect was achieved with MFS-LNCs incorporating CTAB as positive charge imparting agent or oleic acid as membrane permeabilizer. Reduction of worm load, ameliorated liver pathology and extensive damage of the worm tegument provided evidence for formulation-related efficacy enhancement. Non-compartmental analysis of pharmacokinetic data obtained in rats indicated independence of antischistosomal activity on systemic drug exposure, suggesting possible gut uptake of the stable LNCs and targeting of the fluke tegument which was verified by SEM. The study findings put forward MFS-LNCs as unique oral nanovectors combining the bioactivity of MFS and biopharmaceutical advantages of LNCs, allowing targeting via the oral route. From a clinical point of view, data suggest MFS-LNCs as a potential single dose oral nanomedicine for enhanced therapy of schistosomiasis mansoni and possibly other diseases.     

剖宫产术前单剂量头孢三嗪预防感染效果探讨

目的：研究单剂量头孢三嗪在急诊剖宫产手术中预防感染的效果。方法：1998－2000年急诊剖宫产病例399例,分A,B两组,A组201例,于术前30分钟静脉推注头孢三嗪1．0g;B组198例为对照组,采用传统的青霉素静脉点滴方法。结果：两组病例的产褥病率,产褥感染,切口感染的发生率无显著差异,A组术后排气时间较B组早,A组的费用低于B组,结论：单剂量头孢三嗪用于急诊剖宫产手术预防感染疗效好,费用低。     

凯妮汀单次治疗妊娠期念珠菌性阴道病102例临床观察

目的：观察凯妮汀单次治疗妊娠期念珠菌性阴道病的疗效。方法：将早孕期及晚孕期合并念珠菌阴道病的患者102例,给予凯妮汀阴道片1片,置于后穹窿处。用药后7-10天复查。结果：凯妮汀治疗妊娠期念珠菌性阴道病的临床治愈率为79．4％,有效率为13.7％,24小时症状减少率为77．4％。结论：凯妮汀单次治疗对于妊娠期念珠菌性阴道病具有较好的效果。     

Enhanced Activity of Deoxycytidine Kinase After Pulsed Low Dose Rate and Single Dose Gamma Irradiation

In both pulsed low dose rate (LDR) and single high dose radiation schedules, gemcitabine pretreatment sensitizes tumor cells to radiation. These radiosensitizing effects could be the result of decreased DNA repair. In this study, the effect of irradiation on the deoxycytidine kinase (dCK) needed for DNA repair was investigated. The activity of dCK, a deoxynucleoside analogue-activating enzyme was increased upon irradiation in both schedules. No change in dCK protein expression was observed that indicates a post-translational regulation. The benefit of this increased activity induced by irradiation should be further investigated in combination with deoxynucleoside analogues activated by this enzyme.     

Ethchlorvynol (Placidyl) Intoxication and Its Treatment by Hemodialysis

Twenty hours after ingesting 15-25 g. of ethchlorvynol, a 37-year-old woman was admitted comatose and in shock. The blood level of ethchlorvynol was 21.6 mg. % (method of Wallace). Supportive measures were instituted and hemodialysis, carried out for 10 hours, removed 5.49 g. of the drug. The post-dialysis blood level was 9.05 mg. % and the rate of dialysance was 50.5 ml./min. Only 0.6 g. of the substance was recovered from the urine over the same period.Although dialysis removed significant amounts of the drug and sustained life, the patient remained comatose for five days before withdrawal symptoms and seizures developed.     

壳聚糖／海藻酸钠微囊作为口服控释制剂载体的研究

壳聚糖与海藻酸钠通过聚电解质络合反应制备成壳聚糖 /海藻酸钠微囊 ,其粒径为 1mm左右。以干扰素为模型药物 ,其包封率达 90 %以上。同时还研究了在不同 pH条件下 ,干扰素的控制释放情况。结果表明 :微囊在模拟胃液 (pH 1.0 )中 3h的药物释率仅为≤ 5 % ,但在模拟肠液 (pH 7.4 )中 3h ,80 %～ 90 %的药物被释放。     

Rapid Treponema pallidum Clearance from Blood and Ulcer Samples following Single Dose Benzathine Penicillin Treatment of Early Syphilis

Currently, the efficacy of syphilis treatment is measured with anti-lipid antibody tests. These can take months to indicate cure and, as a result, syphilis treatment trials require long periods of follow-up. The causative organism, Treponema pallidum (T. pallidum), is detectable in the infectious lesions of early syphilis using DNA amplification. Bacteraemia can likewise be identified, typically in more active disease. We hypothesise that bacterial clearance from blood and ulcers will predict early the standard serology-measured treatment response and have developed a qPCR assay that could monitor this clearance directly in patients with infectious syphilis. Patients with early syphilis were given an intramuscular dose of benzathine penicillin. To investigate the appropriate sampling timeframe samples of blood and ulcer exudate were collected intensively for T. pallidum DNA (tpp047 gene) and RNA (16S rRNA) quantification. Sampling ended when two consecutive PCRs were negative. Four males were recruited. The mean peak level of T. pallidum DNA was 1626 copies/ml whole blood and the mean clearance half-life was 5.7 hours (std. dev. 0.53). The mean peak of 16S rRNA was 8879 copies/ml whole blood with a clearance half-life of 3.9 hours (std. dev. 0.84). From an ulcer, pre-treatment, 67,400 T. pallidum DNA copies and 7.08x107 16S rRNA copies were detected per absorbance strip and the clearance half-lives were 3.2 and 4.1 hours, respectively. Overall, T. pallidum nucleic acids were not detected in any sample collected more than 56 hours (range 20–56) after treatment. All patients achieved serologic cure. In patients with active early syphilis, measuring T. pallidum levels in blood and ulcer exudate may be a useful measure of treatment success in therapeutic trials. These laboratory findings need confirmation on a larger scale and in patients receiving different therapies.     

A Simple Method for Encapsulating Single Cells in Alginate Microspheres Allows for Direct PCR and Whole Genome Amplification

Microdroplets are an effective platform for segregating individual cells and amplifying DNA. However, a key challenge is to recover the contents of individual droplets for downstream analysis. This paper offers a method for embedding cells in alginate microspheres and performing multiple serial operations on the isolated cells. Rhodobacter sphaeroides cells were diluted in alginate polymer and sprayed into microdroplets using a fingertip aerosol sprayer. The encapsulated cells were lysed and subjected either to conventional PCR, or whole genome amplification using either multiple displacement amplification (MDA) or a two-step PCR protocol. Microscopic examination after PCR showed that the lumen of the occupied microspheres contained fluorescently stained DNA product, but multiple displacement amplification with phi29 produced only a small number of polymerase colonies. The 2-step WGA protocol was successful in generating fluorescent material, and quantitative PCR from DNA extracted from aliquots of microspheres suggested that the copy number inside the microspheres was amplified up to 3 orders of magnitude. Microspheres containing fluorescent material were sorted by a dilution series and screened with a fluorescent plate reader to identify single microspheres. The DNA was extracted from individual isolates, re-amplified with full-length sequencing adapters, and then a single isolate was sequenced using the Illumina MiSeq platform. After filtering the reads, the only sequences that collectively matched a genome in the NCBI nucleotide database belonged to R. sphaeroides. This demonstrated that sequencing-ready DNA could be generated from the contents of a single microsphere without culturing. However, the 2-step WGA strategy showed limitations in terms of low genome coverage and an uneven frequency distribution of reads across the genome. This paper offers a simple method for embedding cells in alginate microspheres and performing PCR on isolated cells in common bulk reactions, although further work must be done to improve the amplification coverage of single genomes.     

Fractioned Dose Regimen of Sunitinib for Patients with Gastrointestinal Stromal Tumor: A Pharmacokinetic and Treatment Efficacy Study

AIM: Sunitinib has shown benefit in patients with imatinib (IM)–resistant gastrointestinal stromal tumor (GIST). However, its advantages are somewhat diminished because of associated toxicities. Herein, we clarify the efficacy and safety of fractioned dose regimen of sunitinib by a pharmacokinetic and efficacy study. MATERIALS AND METHODS: Between 2001 and March 2013, a total of 214 patients with metastatic GIST was treated at Chang Gung Memorial Hospital. Among them, 55 (11.6%) patients who received sunitinib were investigated. One group of patients was administered with standard dose of once-daily sunitinib (standard dose group) and the other group was administered with standard total daily dose of sunitinib in fractioned doses (fractioned dose group). RESULTS: Thirty-two male and 23 female patients with a median age of 55 years received sunitinib. The median duration of sunitinib administration was 9.2 months. The clinical benefit was 65.2%. The mean peak blood level of sunitinib in patients with fractioned doses was significantly lower than that in those with once-daily dose (83.4 vs 50.1 ng/ml, P = .01). The rates of adverse effects of hand-foot syndrome, mucositis, and yellow skin were significantly decreased by fractioned doses of sunitinib. However, the progression-free and overall survival did not differ between patients with different treatment regimens. CONCLUSION: The fractioned dose regimen of sunitinib appears to be a safe and effective treatment for patients with IM-resistant/intolerant GISTs. Significantly decreased toxicity of this regimen could be explained by significantly lower peak sunitinib blood level. However, the treatment efficacy is not reduced by this regimen.     

N-Acetylcysteine Ameliorates Neurotoxic Effects of Manganese Intoxication in Rats: A Biochemical and Behavioral Study

Neurochemical Research - Clinical and experimental evidences reveal that excess exposure to manganese is neurotoxic and leads to cellular damage. However, the mechanism underlying manganese...     

经单侧经皮椎体成形术小剂量与常规剂量骨水泥灌注治疗骨质疏松性椎体压缩骨折的疗效对比研究

摘要 目的：探讨经单侧经皮椎体成形术（PVP）小剂量与常规剂量骨水泥灌注治疗骨质疏松性椎体压缩骨折（OVCF）的疗效。方法：回顾性分析2017年3月~2019年2月期间我院收治的OVCF患者92例,均采用经单侧PVP治疗,根据骨水泥灌注剂量将患者分为A组46例和B组46例,A组给予常规剂量（2.6～3.5 mL）骨水泥灌注,B组给予小剂量（1.5～2.5 mL）骨水泥灌注。对比两组围术期指标、视觉模拟评分表（VAS）和Oswestry功能障碍指数（ODI）评分、Cobb 角和伤椎椎体前缘高度比、骨水泥渗漏情况及其他并发症发生情况。结果：两组术中出血量、手术时间对比无统计学差异（P>0.05）。对比两组术后1个月、术后6个月VAS、ODI评分无差异（P>0.05）,两组术前、术后1个月、术后6个月VAS、ODI评分呈下降趋势（P<0.05）。两组术后1个月、术后6个月Cobb角均较术前减小（P<0.05）。B组术后1个月、术后6个月伤椎椎体前缘高度比较A组更低（P<0.05）。B组渗漏总发生率较A组更低（P<0.05）。对比两组其他并发症无差异（P>0.05）。结论：经单侧PVP小剂量与常规剂量骨水泥灌注治疗OVCF,均可有效改善患者临床症状,减轻疼痛,促进运动功能恢复,但常规剂量骨水泥灌注治疗患者伤椎椎体前缘高度比改善更佳,而小剂量骨水泥灌注渗漏总发生率较低。     

经皮椎间孔镜与椎板开窗椎间盘切除术治疗单节段单侧腰椎间盘突出症的对比研究

目的:探讨经皮椎间孔镜(PTED)与椎板开窗椎间盘切除术(FD)治疗单节段单侧腰椎间盘突出症(LDH)的临床疗效。方法:选取2015年1月-2016年12月来华北石油管理局总医院治疗的120例单节段单侧LDH患者,其中采用PTED术式治疗患者60例,作为PTED组,采用FD术式治疗患者60例,作为FD组。记录两组患者术中出血量、手术时间、切口长度、卧床时间、住院时间以及并发症发生率,比较两组患者术前、术后24 h、术后1周、术后3个月、术后6个月、术后12个月的视觉疼痛模拟(VAS)评分和Oswestry功能障碍指数(ODI)评分,并在术后12个月时采用MacNab疗效评定标准评价治疗效果。结果:PTED组患者在术中出血量、手术时间、切口长度、卧床时间、住院时间、并发症发生率均低于FD组(P0.05)。术后12个月PTED组患者VAS评分、ODI评分均低于FD组(P0.05),术后两组患者的VAS评分、ODI评分随着时间的推移越来越低,且与上一时间点相比均具有统计学差异(P0.05)。PTED组优良率为93.33%,与FD组的91.67%比较差异无统计学意义(P0.05)。结论:两种术式治疗LDH患者的疗效无差异,但是采用PTED术式手术时间短、术中出血量少、创伤小、术后并发症少,在减轻术后疼痛和改善生活能力方面优于FD术式。     

单孔与三孔胸腔镜治疗肺大泡并自发性气胸的临床对比研究

目的:对比肺大泡并自发性气胸患者经单孔与三孔胸腔镜治疗后的临床疗效.方法:回顾性分析2016年6月～2019年4月期间我院收治的93例肺大泡并自发性气胸患者的临床资料,根据手术方式的不同将其分为单孔组(n=45,单孔胸腔镜治疗)和三孔组(n=48,三孔胸腔镜治疗),比较两组患者围术期指标、视觉疼痛模拟量表(VAS)评分...     

Advantages of Repeated Low Dose against Single High Dose of Kainate in C57BL/6J Mouse Model of Status Epilepticus: Behavioral and Electroencephalographic Studies

A refined kainate (KA) C57BL/6J mouse model of status epilepticus (SE) using a repeated low dose (RLD) of KA (5 mg/kg, intraperitoneal; at 30 min intervals) was compared with the established single high dose (SHD) of KA (20 mg/kg, intraperitoneal) model. In the RLD group, increased duration of convulsive motor seizures (CMS, Racine scale stage ≥3) with a significant reduction in mortality from 21% to 6% and decreased variability in seizure severity between animals/batches were observed when compared to the SHD group. There was a significant increase in the percentage of animals that reached stage-5 seizures (65% versus 96%) in the RLD group. Integrated real-time video-EEG analysis of both groups, using NeuroScore software, revealed stage-specific spikes and power spectral density characteristics. When the seizures progressed from non-convulsive seizures (NCS, stage 1–2) to CMS (stage 3–5), the delta power decreased which was followed by an increase in gamma and beta power. A transient increase in alpha and sigma power marked the transition from NCS to CMS with characteristic ‘high frequency trigger’ spikes on the EEG, which had no behavioral expression. During SE the spike rate was higher in the RLD group than in the SHD group. Overall these results confirm that RLD of KA is a more robust and consistent mouse model of SE than the SHD of KA mouse model.     

常规开颅手术和脑室镜治疗硬膜下血肿的对比研究

目的:对比分析常规开颅手术和脑室镜治疗硬膜下血肿的临床疗效。方法:自2012年1月到2013年10月,我科急诊收治的硬膜下血肿病例共63例。其中脑室镜组28例,男16例,女12例,年龄(33.2±9.4)岁;常规开颅组35例,男23例,女12例,年龄30.2±9.4岁。常规开颅组采用传统的大骨瓣开颅术清除颅内血肿,另一组采用脑室镜微创技术清除颅内血肿。结果:脑室镜组和常规开颅组的术前GCS评分分别为4.2±0.7、4.6±0.8,差异无统计学意义(P0.05)。术后第3、7天脑室镜GCS评分明显升高,和常规开颅组相比,差异有统计学意义(P0.05);术后第1、3、7天,脑室镜组的血糖水平明显比常规开颅组下降的速度快,差异具有统计学意义(P0.05);脑室镜组头皮切口长度、骨窗大小明显比常规开颅组要小,血肿清除率大,二者差异有统计学意义;两组预后差异有统计学意义(P0.05)。结论:脑室镜治疗硬膜下血肿,具有手术时间短,创伤小,术后患者恢复速度快等优点,值得推广。