Simultaneous administration of multiple model substrates to assess hepatic drug clearance

We have evaluated a method to simultaneously assess three major processes involved in hepatic drug clearance using three model substrates administered simultaneously as a 5-minute intravenous injection. Lorazepam, indocyanine green, and antipyrine are used to assess conjugation, liver blood flow, and microsomal oxidative metabolism, respectively. These substrates were administered individually and as a mixture to 10 healthy adult male volunteers to determine if clearances of any of the compounds were affected by simultaneous administration. Mean clearances of the substrates were not different when administered alone (9.97, 0.78, and 0.53 ml/min/kg) vs. together (11.5, 0.89, and 0.52 ml/min/kg), using a paired t test. Since we were using this method to assess hepatic drug clearance in children with leukemia, the effect of short-term allopurinol was assessed. The three model substrates were administered to the volunteers after 0, 1, 8, and 22 days of treatment with allopurinol, 200 mg t.i.d. There was no change in mean clearance of any of the three compounds at any point during allopurinol treatment (repeated-measures ANOVA). We conclude that this technique is a simple and valid method to simultaneously assess three major processes involved in hepatic drug clearance and is not affected by up to 22 days of oral allopurinol treatment. This simple technique, requiring a single set of blood samples, has potential applications in the assessment of developmental changes in hepatic drug clearance, as well as the effects of environmental, therapeutic, and pathophysiologic factors on three major processes involved in hepatic drug clearance.     

Age-related differences in hepatic drug clearance in children: studies with lorazepam and antipyrine

The disposition of intravenous antipyrine and lorazepam, administered as model substrates for hepatic oxidative metabolism and conjugation, was evaluated in 50 children (mean age, 7.8 years; range, 2.3 to 17.8 years) with acute lymphocytic leukemia in complete remission and compared with a group of ten healthy adults. Antipyrine clearance normalized to body weight was significantly greater in children than in adults (0.91 versus 0.59 ml/min/kg; p = 0.012), but was not different when normalized to body surface area. In contrast, lorazepam total clearance (CL) and unbound clearance (CLu) normalized to body weight were not significantly different between children and adults but were smaller in children when normalized to body surface area (CL = 31.9 versus 40.6 ml/min/m2, p = 0.036; CLu = 352 versus 485 ml/min/m2, p = 0.010). The mean lorazepam fraction unbound in children was 0.087, which was not different from adult volunteers (0.084). This study has identified significant differences between children and adults in the disposition of these two compounds, with higher milliliter per minute per kilogram clearance for antipyrine but not lorazepam.     

Systemic Candida infections in patients with leukemia: an overview of drug therapy

Systemic fungal infections are becoming increasingly common in patients with hematologic malignancies receiving antineoplastic therapy. The presence of acute myeloid or acute lymphoid leukemia, plus the use of chemotherapy to totally ablate malignant bone marrow cells, puts patients in a protracted neutropenic state. During this profound and prolonged neutropenic phase, patients receive antibiotic therapy for suspected or identified bacterial infections. However, when fever or other signs of infection continue despite antibiotic therapy, patients frequently need to be treated for suspected or identified systemic fungal infections. These infections may occur in patients receiving either standard antileukemia therapy or research protocol therapy involving new drugs, new drug combinations, higher doses, or newer schedules of established drugs. After antifungal therapy is initiated, it may be continued postdischarge in outpatient or homecare settings. Therefore, becoming knowledgeable about antifungal therapy is important for all oncology nurses regardless of practice setting.     

The sieving coefficient and clearance of vasopressin during continuous renal replacement therapy in critically ill children

HypothesisAs vasopressin is a small peptide, its sieving coefficient (SC) and clearance (CL) during continuous renal replacement therapy may be intermediate to those for urea and β2 microglobulin (commonly used markers for small– and middle–molecular weight solutes, respectively).MethodsA prospective, minimal-risk study was undertaken of the SC and CL of vasopressin in critically ill children on the first day of continuous renal replacement therapy using AN69 membrane filters and prefilter replacement fluid. All prefilter plasma (vasopressin) samples were drawn from the arterial port after predilution.ResultsNine patients with fluid overload, renal failure, or both were recruited (median age, 14 years) during the first day of either continuous venovenous hemofiltration (n = 3) or hemodiafiltration (n = 6). Multiorgan dysfunction syndrome was present in 8 patients, and 3 were in shock (2 were receiving a vasopressin infusion). Median prefilter plasma (vasopressin) was 1.7 pg/mL, although data points were skewed: 5 patients had a low prefilter plasma (vasopressin) (<2 pg/mL), and 4 patients (including 2 receiving a continuous vasopressin infusion) had a prefilter plasma (vasopressin) between 4.2 and 56.4 pg/mL. All those with low prefilter plasma (vasopressin) had an effluent (vasopressin) less than the detection limit (0.6 pg/mL). The median SC was 1 in the 4 patients with a measurable effluent (vasopressin), and their median filter CL was 48 mL/min or 39 mL/(min 1.73 m²).ConclusionsThe SC and CL of vasopressin by continuous venovenous hemofiltration or hemodiafiltration in these critically ill children were similar to values for urea.     

The relevance of plasma lipid changes with cardiovascular drug therapy

Evidence is reviewed that thiazide diuretics increase plasma levels of triglycerides and LDL-cholesterol, and that most beta-blockers increase triglycerides and depress HDL-cholesterol. By contrast, indapamide, pindolol, and calcium channel blockers have little effect, and alpha 1-blockers and alpha 2-stimulants may improve the HDL- to LDL-cholesterol ratio.     

Effect of saturable clearance during high-dose mezlocillin therapy.

As mezlocillin has been shown to display nonlinear pharmacokinetics in single-dose evaluations, we evaluated a crossover trial in patients with renal dysfunction the impact on serum clearance of fixed-dose versus fixed-interval administration of identical daily doses of the drug. In four patients with creatinine clearances of 0.00 to 1.78 liters/h per 1.73 m2, equal serum clearances were observed when the calculated daily total dose of mezlocillin was given either as a fixed dose of 5,000 mg at various intervals or every 4 h at various doses. We found that repetitive large daily doses that are equivalent to 30 g/day in patients with normal renal function can be administered to patients with impaired renal function as a reduced dose every 4 h instead of prolonging the dosing interval, as suggested by Mangione et al. (Antimicrob. Agents Chemother. 21:428-435, 1982). The observed serum clearances were equal for the two schedules, probably owing to the degree of continuing saturation of the nonlinear clearance mechanisms of mezlocillin.     

家长参与的绘画疗法在白血病患儿中的应用研究

目的 探讨家长参与的绘画疗法对白血病患儿心理状态、家庭功能及生活质量的影响。方法 采用非同期对照临床试验设计,便利选取2021年7月—2022年1月安徽省某三级甲等肿瘤专科医院收治的40例白血病患儿及其家长作为试验组,在常规护理的基础上接受家长参与的绘画疗法;将2020年12月—2021年6月收治的40例白血病患儿及其家长作为对照组,予以常规护理。于干预前及干预3、6周后,采用中文版儿童焦虑性情绪障碍筛查表、儿童抑郁障碍自评量表、家庭亲密度和适应性量表、儿童生存质量癌症模块量表评估两组患儿的焦虑水平、抑郁水平、家庭功能及生活质量。结果 共脱落6例,最终试验组36例、对照组38例完成研究。两组不同时间点焦虑水平、家庭功能比较,时间效应、组间效应及交互效应均具有统计学意义（P<0.05）;抑郁水平、生活质量比较,时间效应、组间效应及交互效应均无统计学意义（P>0.05）。简单效应分析结果显示,干预3、6周后试验组焦虑水平低于对照组,干预6周后试验组家庭功能优于对照组,差异具有统计学意义（P<0.05）。结论 实施家长参与的绘画疗法可有效减轻白血病患儿的焦虑情绪,改善其家庭...     

左旋门冬酰胺酶脱敏法治疗7例小儿急性淋巴细胞白血病的护理

左旋门冬酰胺酶是治疗急性淋巴细胞白血病的关键药物之一,可以提高疾病的缓解率和患儿生存率,但过敏反应常见。报告了我院儿科2003年3月至2005年12月共7例使用左旋门冬酰胺酶出现变态反应的患儿实施脱敏注射法的护理,总结脱敏过程中护理工作要点,包括左旋门冬酰胺酶皮试的观察;脱敏过程中的症状观察和应对措施;心理支持;用药后的密切观察,严防迟发反应发生。7例脱敏注射治疗均获成功。     

Physical therapy for airway clearance improves cardiac autonomic modulation in children with acute bronchiolitis

Background

The effects of physical therapy on heart rate variability (HRV), especially in children, are still inconclusive.

Objective

We investigated the effects of conventional physical therapy (CPT) for airway clearance and nasotracheal suction on the HRV of pediatric patients with acute bronchiolitis.

Method

24 children were divided into two groups: control group (CG, n=12) without respiratory diseases and acute bronchiolitis group (BG, n=12). The heart rate was recorded in the BG at four different moments: basal recording (30 minutes), 5 minutes after the CPT (10 minutes), 5 minutes after nasotracheal suction (10 minutes), and 40 minutes after nasotracheal suction (30 minutes). The CG was subjected to the same protocol, except for nasotracheal suction. To assess the HRV, we used spectrum analysis, which decomposes the heart rate oscillations into frequency bands: low frequency (LF=0.04-0.15Hz), which corresponds mainly to sympathetic modulation; and high frequency (HF=0.15-1.2Hz), corresponding to vagal modulation.

Results

Under baseline conditions, the BG showed higher values in LF oscillations, lower values in HF oscillations, and increased LF/HF ratio when compared to the CG. After CPT, the values for HRV in the BG were similar to those observed in the CG during basal recording. Five minutes after nasotracheal suction, the BG showed a decrease in LF and HF oscillations; however, after 40 minutes, the values were similar to those observed after application of CPT.

Conclusions

The CPT and nasotracheal suction, both used for airway clearance, promote improvement in autonomic modulation of HRV in children with acute bronchiolitis.     

急性白血病患儿化疗期间症状群的调查分析

目的 了解急性白血病患儿化疗期间的症状发生情况,探讨其症状群的种类和数量。 方法 采用儿童版记忆症状评估量表对 165 例急性白血病患儿进行问卷调查,比较 2 种探索性因子分析法结果,并结合聚类分析及 Spearman 秩相关分析,最终确定患儿症状群。 结果 急性白血病患儿化疗期间的主要症状为出汗、容易发怒或急躁、缺乏活力（疲乏）、没有食欲。 患儿存在 6 组症状群,分别为神经心理不适症状群、头部相关症状群、胃肠道相关症状群、自我形象受损相关症状群、口腔相关症状群、皮肤瘙痒 - 腹泻相关症状群, Cronbach蒺s α 系数依次为 0.96 、 0.80 、 0.75 、 0.67 、 0.76 、 0.62 。 结论 急性白血病患儿化疗期间存在多种症状群。医护人员可以以症状群为基础探索具有针对性的干预模式,可产生更好的干预效果。     

Hemostatic changes during the treatment of acute promyelocytic leukemia with all-transretinoic acid

AIM: To study hemostasis in ATRA treatment of acute promyelocytic leukemia (APL). MATERIAL AND METHODS: Hemostasis was studied in 8 newly admitted APL patients treated with ATRA. All of them had hemorrhages, thrombocytopenia 5-15 x 10(9)/l at diagnosis, laboratory signs of the DIC syndrome at induction therapy. RESULTS: Hemorrhage arresting was seen on the ATRA therapy day 14 to 30. Duration of thrombocytopenia under 20 x 10(9)/l was 5.8 +/- 1.8 days. After 7 days of ATRA therapy coagulation tests improved with some hypercoagulation tendency. Subsequent condition of hemostasis was considered as normo/hypercoagulation accompanied by constant thrombin persistence (in the presence of FDP) and depression of hageman-dependent fibrinolysis even in remission. A case of ileofemoral thrombosis followed by fatal thromboembolism of the pulmonary artery is reported. CONCLUSION: It is suggested to use heparin, especially low molecular weight heparin when there are signs of hypercoagulation in APL patients.