An 11-year review of bupropion insufflation exposures in adults reported to the California Poison Control System

Background. Seizures of both immediate and delayed onset after ingestion of bupropion SR and bupropion XL formulations are well documented, but are less well characterized after insufflation. Bupropion is crushed and insufflated to experience a high similar to that from amphetamines and cocaine. We sought to characterize the abuse of bupropion via insufflation in cases reported to the California Poison Control System (CPCS) and the incidence of seizures. Methods: An 11-year (2002–2012) retrospective observational case series of insufflated bupropion exposures evaluated in a health care facility (HCF) were reviewed after searching our database for all bupropion insufflation exposures. Patients with coingestants, multiple exposure routes, or age less than 18 were excluded. Data included age, gender, estimated bupropion dose, occurrence of pre-HCF seizures, symptoms and vital signs reported to the CPCS, treatments, and adverse events that occurred until time of discharge. Results: 74 cases were identified (1 excluded due to age, 5 excluded due to additional oral ingestion of bupropion, and 1 excluded due to being unable to follow). A total of 67 cases met inclusion criteria. The median age was 36 (range, 18–65) years. The total dose of bupropion insufflated was reported in 52 pts; median dose of 1500 (range, 100–9000) mg. Eighteen cases (27%) involved staggered or chronic exposures. Of the 67 patients, 20 (30%) experienced a seizure prior to arrival at the HCF. Of these, 19 patients (95%) presented with tachycardia. None of these patients had a second seizure in the emergency department. There were no major medical outcomes and no deaths. Of the 67 patients, 9 patients received benzodiazepines and 6 patients received single-dose activated charcoal. Conclusion: The abuse of bupropion by crushing and insufflating through the nose is uncommon (67/2270 or 3.0%) compared with that by oral bupropion exposures reported to CPCS. Seizures are common but are self-limited. Delayed seizures (more than 8 h after exposure) appear to be rare. Tachycardia is present in almost all patients who have seizures.     

Delayed recovery associated with persistent serum concentrations after clozapine overdose

Experience with managing overdoses of the atypical antipsychotic agent, clozapine, has been limited. A 20-year-old woman, who presented 6 h after ingesting 3500 mg of clozapine, had an unexpectedly prolonged duration of tachycardia and somnolence. Successful recovery followed management with supportive measures for several days in the intensive care unit. However, the duration of symptoms greatly exceeded that predicted by the published 12-h half-life of clozapine and was associated with an unexplained persistence of serum clozapine concentrations. Recovery with normalization of autonomic function occurred only after serum clozapine began to decline again after a 4-day plateau, as revealed by serum monitoring. Similar observations have been reported in two other cases. In overdose, clozapine may not behave as predicted by its published pharmacokinetics. Persistent serum drug concentrations may prolong the period of intensive care, suggesting that aggressive measures to remove clozapine from the gut at the time of overdose may be warranted.     

Epirubicin cardiotoxicity: A study comparing low- with high-dose-intensity weekly schedules

Epirubicin is one of the less cardiotoxic alternatives to doxorubicin. We were interested in studying the cardiotoxic effect of the total cumulative dose, and weekly schedules of low compared to high dose intensity. Fifty-seven patients were treated with different epirubicin-containing regimens. We confirm the classical notion that total cumulative doses of less than 600 mg/m² do not induce significant cardiotoxicity, whereas doses above 600 mg/m² are associated with a trend towards cardiotoxicity. Patients receiving a high weekly dose intensity ( > 40 mg/m²), however, did have a significantly lower incidence of cardiotoxicity than those receiving a low dose intensity per week (<40 mg/m²) (22.8% versus 50%;P<0.05). We identified the association of a dose intensity of more than 40 mg m^–2/week^–1 and a cumulative dose of 400–899 mg/m² or a dose intensity of less that 40 mg m^–2/week^–1 and a cumulative dose of less than 400 mg/m² to have the lowest incidence rate of cardiotoxicity. We conclude from this study that epirubicin in weekly schedules of high dose intensity is not more cardiotoxic than in weekly schedules of low dose intensity.     

Low serum bilirubin concentrations are associated with impaired aortic elastic properties, but not impaired left ventricular diastolic function

Elevated serum bilirubin concentrations protect from atherosclerotic diseases; however, it is not clear whether higher serum bilirubin concentrations in physiological ranges do the same. To investigate the association of high and low serum bilirubin concentrations with left ventricular diastolic function and aortic elastic properties. We evaluated left ventricular diastolic function and aortic elastic properties of 42 healthy subjects with hypobilirubinemia (total bilirubin 0.40 ± 0.08 mg/dl; mean age 37.0 ± 3.9) and 40 healthy subjects with hyperbilirubinemia (total bilirubin 1.56 ± 0.49 mg/dl; mean age 36.2 ± 6.0) using transthoracic second harmonic Doppler echocardiography. Age, gender, body mass index and coronary risk factors were similar between the groups, except high‐sensitivity C‐reactive protein (hsCRP). Left ventricular diastolic parameters were similar between the two groups. Aortic distensibility (AoD) was found to be significantly lower (11.1 ± 3.9 vs. 13.2 ± 4.9, p = 0.03) and aortic stiffness index (AoSI) (1.99 ± 0.30 vs. 1.85 ± 0.26, p = 0.02) and elastic modulus (AoEM) (2.06 ± 0.83 vs. 1.73 ± 0.68, p = 0.03; the low and high bilirubin groups, respectively) higher in the low bilirubin group. Serum total bilirubin concentration correlated with hsCRP levels, AoD, AoSI and AoEM. In conclusion, left ventricular systolic and diastolic functions were similar between hypo‐ and hyperbilirubinemic subjects, but aortic elastic properties were impaired in subjects with lower serum bilirubin concentrations.     

Hyaluronan serum concentrations are elevated in critically ill patients and associated with disease severity

ObjectivesThe matrix protein hyaluronic acid (HA, hyaluronan) has possibly additional immune-regulatory functions in inflammation. We aimed at evaluating serum HA concentrations in critically ill patients.Design and methodsWe analyzed serum HA levels in 164 critically ill patients at a medical ICU and 61 healthy controls, with respect to organ dysfunction, systemic inflammation and mortality.ResultsHyaluronan serum concentrations upon admission to ICU were significantly elevated in critically ill patients compared to healthy controls, with the highest levels in patients with pre-existing liver cirrhosis or sepsis. HA levels were closely correlated with biomarkers of hepatic and renal function, systemic inflammation, demand of treatment measures and clinical scores of disease severity, but could not predict risk of mortality.ConclusionsMeasurement of serum HA may supplement the assessment of disease severity in ICU patients. Our data suggest that HA might have implications in the pathogenesis of critical illness and sepsis.     

蒽环类抗生素导致儿童急性白血病化疗严重心脏毒性的临床分析

目的总结急性白血病患儿使用蒽环类抗生素化疗致严重心脏毒性的临床特征及预后。方法收集2003年1月至2009年3月血液病区发生的蒽环类抗生素相关严重心脏毒性的14例急性白血病患儿的临床资料,回顾分析其严重心脏毒性发生的时间、临床表现、实验室检查、治疗及转归。结果14例患儿心脏毒性发生时间为应用最近一次蒽环类抗生素后5—12d。蒽环类药物累积剂量为（以柔红霉素计）（134．8±56．6）mg／m^2。严重心脏毒性全部为亚急性,合并细菌感染13例。心电图均存在明显异常,超声心动图指标变化用药前后无显著差异（P〉0．05）。抢救成功10例。结论儿童急性白血病蒽环类抗生素化疗合并感染时严重心脏损害的发生率高,抢救成功病例恢复良好。     

二维斑点追踪成像评价乳腺癌曲妥珠单抗化疗亚临床心脏毒性的价值

目的应用二维斑点追踪成像(2D-STI)评估乳腺癌患者曲妥珠单抗化疗周期中心室收缩功能的早期改变,探讨2D-STI在评价化疗相关早期亚临床心脏毒性中的应用价值。方法选取在我院接受曲妥珠单抗化疗的HER-2阳性乳腺癌患者89例,共行3个化疗周期(即T1、T2、T3期),每个化疗周期为3周;根据患者化疗期间是否发生心脏毒性分为心脏毒性组22例和无心脏毒性组67例。于化疗前(T0期)和T1、T2、T3期分别行超声心动图检查,测量左室和右室常规超声心动图参数;应用2D-STI测量左室和右室整体纵向峰值应变(LVGLS、RVGLS)、左室周向峰值应变(LVGCS)。以化疗过程中出现心脏毒性为临床结局,应用Logistic回归分析和ROC曲线分析T1期时各参数对化疗亚临床心脏毒性的预测价值。结果心脏毒性组T2、T3期左室射血分数(LVEF)及T1、T2、T3期LVGLS、LVGCS、RVGLS均明显低于无心脏毒性组,差异均有统计学意义(均P<0.05)。心脏毒性组T2期LVEF低于T0期的18%,T1期、T2期LVGLS、LVGCS和RVGLS均显著低于T0期,差异均有统计学意义(P<0.05)。ROC曲线和Logistic回归分析表明T1期RVGLS联合LVGLS是预测乳腺癌化疗相关早期亚临床心脏毒性的最佳指标,其诊断敏感性为98%,特异性为75%。结论无明显LVEF降低的曲妥珠单抗化疗乳腺癌患者,其T1期LVGLS和RVGLS均已减低,2D-STI有助于早期发现化疗相关的亚临床心脏毒性,对改善乳腺癌患者临床结局和预后具有重要临床价值。     

抗肿瘤治疗所致心脏毒性的研究进展

随着肿瘤治疗手段的进展,肿瘤患者的生存时间与生存质量得到了极大的改善,与此同时,细胞毒类药物及靶向治疗等新型抗肿瘤治疗所导致的心血管事件也与日俱增,并且影响着肿瘤患者的生存率与死亡率,由此引起了越来越多学者的关注。在此基础上,肿瘤心脏病学应运而生,其是一门旨在研究肿瘤患者心脏病诊断与治疗的新兴学科,其中抗肿瘤治疗所致心脏疾病是研究重点。笔者主要对抗肿瘤治疗所致心脏毒性的最新研究进展作一综述。     

舒血宁治疗阿霉素引起的心脏毒性的临床研究

目的探讨舒血宁对恶性肿瘤患者应用阿霉素引起的心脏毒性的防治作用。方法选择2010年3月至2012年12月收治的恶性肿瘤患者80例,全部患者按实际就诊顺序随机分为研究组和对照组。两组患者均给予含阿霉素化疗方案治疗,其中研究组患者每个化疗周期前额外加用舒血宁静脉滴注,每日一次,持续治疗2周。观察两组治疗后心肌酶谱及心电图改变情况,评价舒血宁对阿霉素引起的心脏毒性的防治作用。结果治疗后研究组肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(c Tn I)、乳酸脱氢酶(LDH-1)及C反应蛋白(CRP)水平明显低于对照组,两组差异有统计学意义;治疗中研究组异常心电图情况明显少于对照组,差异有统计学意义(P0.05)。结论舒血宁辅助化疗可减轻阿霉素的心脏毒性,利于阿霉素化疗剂量的维持,保证了化疗效果,推荐在临床推广和应用。     

Gestational diabetes mellitus is associated with increased C-reactive protein concentrations in the third but not second trimester

OBJECTIVE: Serum C-reactive protein (CRP) concentrations were measured longitudinally throughout pregnancy to test the hypothesis that CRP could relate more closely to glucose tolerance than to adiposity. METHODS: The CRP concentrations in pregnant women with normal glucose tolerance (NGT) and those with gestational diabetes mellitus (GDM) were measured at the same time as the oral glucose tolerance test (OGTT), at the 24th and 28th weeks of gestation and between the 37th and 38th weeks of gestation. RESULTS: At the end of the third trimester, women with GDM had significantly higher CRP levels than women with NGT [median (interquartile range), 9.7 mg L(-1) (5.4-16.0) and 5.7 mg L(-1) (5.1-7.2); P < 0.001, respectively], but at the time of the diagnostic OGTT no significant difference between the two groups was observed. This was owing to a significant increase of CRP in women with GDM between the time of the OGTT and the 37th-38th gestational weeks [median (interquartile range), 1.9 mg L(-1) (-2.2, 6.7); P = 0.01]; whereas, no change in CRP was found in women with NGT [median (interquartile range), -0.1 mg L(-1) (-2.4, 3.1); P = 0.76]. Multiple linear regression analysis showed only a significant independent influence of GDM (P < 0.001) on maternal CRP concentrations in the 37th-38th gestational weeks and a significant influence of body mass index (P < 0.007), but no influence of GDM at the time of the OGTT. CONCLUSION: These data suggest that in women with gestational diabetes the CRP concentration is primarily related to the degree of adiposity until the second trimester and that thereafter impaired glucose metabolism appears to be the predominant predictor of changes in CRP.     

Low serum 25-hydroxyvitamin D levels are associated with perennial allergic rhinitis but not disease severity

BackgroundVitamin D deficiency plays an essential role in allergic rhinitis(AR), but the role of vitamin D deficiency in perennial allergic rhinitis (pAR) remains unclear. Therefore, our study explored 25(OH)D levels in patients with pAR and healthy individuals in a single center in China for three years.MethodsA total of 655 patients with pAR and 682 healthy controls were enrolled in this study from 2015 to 2017. Patients'' clinical history and symptoms were recorded. sIgE tests were performed using the allergen detection system (UniCAP), and the ADVIA centaur XP system (SIEMENS) was used to measure serum 25(OH)D levels.ResultsSerum 25(OH)D levels were significantly different between the pAR group and control group over the three‐year study period(all P < .05). Specifically, 25(OH)D levels were decreased in the pAR groups over three years. Serum25(OH)D deficiency, insufficiency, and sufficiency were noted in 66.9% ~71.9%, 22.5% ~29.4%, and 2.5%~5.6%, respectively, of patients in the pAR group and 53.2%~60.7%, 31.4%~36.6%, and 7.9% ~11.4%, respectively, of participants in the control group. We did not identify significant associations between serum 25(OH)D levels and clinical characteristics of patients with pAR over the three‐year period (all P > .05) after adjusting for sex, age, duration of disease, total nasal symptom score (TNSS), sIgE levels, number of positive allergens, and family history.ConclusionpAR patients exhibited lower serum 25(OH)D levels compared with healthy people with a high prevalence of 25(OH)D deficiency or insufficiency. We did not identify a significant correlation between 25(OH)D and pAR associated factors.     

Moderately elevated serum troponin concentrations are associated with increased morbidity and mortality rates in surgical intensive care unit patients

OBJECTIVE: To determine the significance of moderate elevations of serum troponin I in a surgical intensive care unit patient population in terms of its impact on indexes of outcome including mortality, morbidity, and hospital and intensive care unit length of stay. DESIGN: Retrospective chart review and analysis of clinical data. SETTING: A surgical intensive care unit at a tertiary care hospital. PATIENTS: From the 27-month surgical intensive care unit database of admissions, 869 patients with serum troponin I determinations during their admission were identified. Patients who had cardiac surgery were excluded. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients were divided into four groups based on their maximum serum troponin I concentrations. Hospital mortality, incidence of myocardial infarction, and hospital and intensive care unit length of stays were compared. Patients with moderate elevations of serum troponin I (0.4-2.0 microg/L) had a significantly higher mortality rate (chi-square = 32.57, p <.0001) and longer length of intensive care unit and hospital stays (p <.0005) when compared with patients without similar elevations. Within the range of moderately elevated troponin concentrations, higher titers were associated with increasing mortality risk, longer hospital and intensive care unit stays, and a higher incidence of myocardial infarction. The use of a beta-blocker and aspirin was associated with better survival for patients with maximum serum troponin concentrations > or =2 microg/L. CONCLUSION: Moderate elevations of serum troponin I, which are below the threshold required to diagnose overt myocardial infarction, may reflect ongoing myocardial injury in the critically ill and are associated with a higher mortality rate and longer hospital and intensive care unit length of stays. The use of beta-blockers and aspirin is associated with better outcomes for this subset of patients.     

单光子发射计算机断层扫描评价阿霉素对非霍奇金淋巴瘤患者的心肌毒性(附44例分析)

目的 :探讨 SPECT心功能测定评价非霍奇金淋巴瘤 (NHL )化疗后阿霉素 (ADM)心肌毒性的可行性。方法 :选择无心脏病基础的 4 4例 NHL患者作研究对象 ,采用常规 CHOP方案进行治疗。定期用 SPECT检测患者的心功能。结果 :化疗前后射血分数 (EF)、高峰射血率 (PER)和高峰充盈率 (PER)值比较 ,差别有显著性 (P<0 .0 5 ) ;体内 ADM累积量愈大 ,EF、PER和 PER值下降愈大 ,并以 PFR变化最敏感。结论 :SPECT心功能测定是评价 NHL患者 ADM心肌毒性的敏感、适用的方法。     

Patient with markedly elevated CA 19-9 not associated with malignancy

A 66-year-old white male presented with jaundice, pruritus, and a 30-pound weight loss over two months. Physical examination revealed scleral icterus. Laboratory evaluation revealed ALT 161 U/L, AST 290 U/L, alkaline phosphatase 2004 U/L, GGT 2,552 U/L, total bilirubin 10.2 mg/dL, and a carbohydrate antigen 19-9 (CA 19-9) level of 4,374 U/mL. Initial endoscopic retrograde cholangiopancreatography (ERCP) was unsuccessful due to ulceration in the duodenum healed with esomeprazole therapy. Subsequent ERCP showed a possible filling defect in the common bile duct treated with sphincterotomy and balloon sweeping of the common bile duct. Symptoms and jaundice resolved five months after initial presentation with normal labs and studies. While elevated CA 19-9 levels occur in most patients with carcinoma of the pancreas, it can also be elevated in patients with extrapancreatic malignancies and acute cholangitis. This case illustrates the fact that a markedly elevated CA 19-9 can be secondary to causes other than carcinoma.     

Association of the Pro90Ser CD36 mutation with elevated free fatty acid concentrations but not with insulin resistance syndrome in Japanese.

BACKGROUND: CD36 deficiency is reportedly an underlying factor about insulin resistance, defective fatty acid metabolism and hypertriglyceridemia in spontaneously hypertensive rat (SHR), and may be involved in the pathogenesis of insulin resistance and hyperlipidemia in humans. METHODS: We examined 831 adults undergoing health screening. The majority (780) was Pro90 homozygous for the CD36 gene product, but 51 displayed a CD36 mutation (2 homozygous and 49 heterozygous for Ser90). This is the major mutation site involved in CD36 deficiency in Japanese. RESULTS: Among parameters related to insulin resistance, there were no differences in body mass index (BMI), HDL cholesterol, total cholesterol, triglycerides, insulin and insulin resistance index (HOMA IR), or blood pressure between 91 normal subjects (45 male and 46 female) randomly selected from the 780 Pro90 homozygotes and the 51 (29 male and 22 females) CD36-deficient subjects (Ser90 homozygote and Pro90Ser heterozygote). Free fatty acid concentrations, however, were higher in Ser90 CD36 subjects than in Pro90 control subjects. CONCLUSIONS: The CD36Pro90Ser mutation is not necessarily related to the insulin resistance syndrome, but is associated with high free fatty acid concentrations in Japanese.     

Chemokine CXC Ligand 16 serum concentration but not A181V genotype is associated with atherosclerotic stroke

BackgroundSerum chemokine CXC Ligand 16 (CXCL16) concentration is associated with atherosclerosis and CXCL16 expression may be influenced by the polymorphism, A181V. We established whether serum CXCL16 concentration or the A181V genotype is more strongly associated with atherosclerotic stroke and its associated risk factor, carotid atherosclerosis.MethodsPCR–RFLP was used to genotype 244 atherosclerotic stroke patients (AS group), 153 stroke-free controls (patient controls) and 167 healthy controls. Serum CXCL16 concentration was determined for a subset of patients (n = 135) and all controls. The same subset of patients was then examined using ultrasound to evaluate their carotid atherosclerotic lesions, including intima-media thickness (IMT), plaque stability and carotid plaque area (CPA).ResultsCompared with the patient controls and healthy controls, serum CXCL16 concentration was significantly increased in the AS group (P < 0.05, and 0.01). It was also strongly associated with increased IMT, vulnerable plaque and increased CPA (P < 0.05, < 0.001, and < 0.01). However, the CXCL16 A181V genotype distribution and allele frequencies showed no differences between AS and control groups, nor did it influence serum CXCL16 concentration.ConclusionSerum CXCL16 concentration is significantly associated with atherosclerotic stroke and carotid atherosclerosis, suggesting that this biochemical test may be useful to identify patients at increased risk of atherosclerosis.     

Plasma concentrations but not serum concentrations of brain-derived neurotrophic factor are related to pro-inflammatory cytokines in patients undergoing major abdominal surgery

ObjectivesTo investigate peripheral brain-derived neurotrophic factor (BDNF) concentrations in the perioperative period, their relationship with transforming growth factor-β1 (TGF-β1 tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-6 genetics.Design and methodsProspective, observational study. BDNF, TGF-β1, IL-6 and TNF-α were analysed at baseline (T0), 5 h (T1), 24 h (T2) and 5 days (T3) after surgery, in 21 patients. The IL-6 ? 174 G/C polymorphism was genotyped.ResultsSerum BDNF concentrations decreased (P = 0.048), correlated with TGF-β1 (r = 0.610 at T1, r = 0.493 at T2, r = 0.554 at T3). Plasma BDNF concentrations raised (P = 0.049), correlated with IL-6 and TNF-α at T1 (r = 0.495 and r = 0.441, respectively). BDNF response was predictable from TNF-α and IL-6 concentrations and the IL-6 ? 174 G/C genotype.ConclusionSerum and plasma BDNF concentrations could relate to platelet activation and inflammatory response, respectively. IL-6 genetics played a role in the BDNF acute response.