Cremophor-induced lupus erythematosus-like reaction with taxol administration: a case report and review of the literature

We report the first case of Cremophor EL-induced cutaneous lupus erythematosus-like reaction in a 40-year-old female undergoing treatment for breast cancer. There have been four reported cases of paclitaxel- and four cases of docetaxel-induced cutaneous lupus reactions in the published literature [Dasanu and Alexandrescu: South Med J 2008;101:1161-1162; Adachi and Horikawa: J Dermatol 2007;34:473-476; Lortholary et al: Presse Med 2007;36:1207-1208; Chen et al: J Rheumatol 2004;31:818-820]. Our patient developed findings of a cutaneous lupus-like reaction with administration of paclitaxel which was subsequently discontinued. She was re-challenged with albumin-bound paclitaxel which has no Cremophor EL compound in its formulation. This administration of albumin-bound paclitaxel did not induce further reaction. She did not develop a cutaneous lupus erythematosus-like reaction with three other subsequent administrations of albumin-bound paclitaxel. The diagnosis of lupus-like reaction in our patient was made based on the development of a malar butterfly rash sparing the nasolabial folds, the appearance of this rash in context of recently receiving treatments with paclitaxel, resolution of the rash after discontinuing the paclitaxel, and the presence of autoimmune antibodies in the patient's serum which resolved with discontinuation of the paclitaxel. This is the first case demonstrating that the cause of the cutaneous lupus erythematosus-like reaction is not likely due to the taxane component of paclitaxel but the chemical composition of Cremophor EL. If the chemotherapeutic agent was causing the reaction then the same reaction should be seen by albumin-bound paclitaxel. We propose that previously reported lupus reactions may actually be due to Cremophor EL, which consists of polyoxyethylated castor oil, and not the chemotherapeutic agent itself.     

同种免疫性与非免疫性血小板减少症新生儿的临床及诊断比较

胎儿和新生儿同种免疫性血小板减少症(alloimmune thrombocytopenia,AIT)的发生是由于胎儿的血小板特异性抗原刺激母体产生同种抗体而引起的。胎儿的这种特异性抗原来源于父亲。通常,胎儿和新生儿发生严重AIT绝大多数是由于胎儿-母体PIA1抗原不相容所致,估计这种病例有20％可并发颅内出血。最近,在挪威和苏格兰进行的AIT发生率的前瞻性研究中发现因PIA1所致的新生儿AIT的发病率大约是1％。由于AIT与其他病因引起的新生儿血小板减少症的治疗方法不同,故对AIT的快速诊断将有助于患儿获得最佳治疗。本研究比较了血清学诊断为AIT的新生儿与血清学不支持诊断为     

Coinfection with hepatitis C virus,oxidative stress and antioxidant status in HIV‐positive drug users in Miami*

Background

The pathogenesis of HIV/hepatitis C virus (HCV) coinfection is poorly understood. We examined markers of oxidative stress, plasma antioxidants and liver disease in HIV/HCV‐coinfected and HIV‐monoinfected adults.

Methods

Demographics, medical history, and proof of infection with HIV, hepatitis A virus (HAV), hepatitis B virus (HBV) and HCV were obtained. HIV viral load, CD4 cell count, complete blood count (CBC), complete metabolic panel, lipid profile, and plasma concentrations of zinc, selenium, and vitamins A and E were determined. Malondialdehyde (MDA) and glutathione peroxidase concentrations were obtained as measures of oxidative stress. Aminotransferase to platelet ratio index (APRI) and fibrosis index (FIB‐4) markers were calculated.

Results

Significant differences were found between HIV/HCV‐coinfected and HIV‐monoinfected participants in levels of alanine aminotransferase (ALT) (mean±standard deviation: 51.4±50.6 vs. 31.9±43.1 U/L, respectively; P=0.014), aspartate aminotransferase (AST) (56.2±40.9 vs. 34.4±30.2 U/L; P<0.001), APRI (0.52±0.37 vs. 0.255±0.145; P=0.0001), FIB‐4 (1.64±.0.91 vs. 1.03±0.11; P=0.0015) and plasma albumin (3.74±0.65 vs. 3.94±0.52 g/dL; P=0.038). There were no significant differences in CD4 cell count, HIV viral load or antiretroviral therapy (ART) between groups. Mean MDA was significantly higher (1.897±0.835 vs. 1.344± 0.223 nmol/mL, respectively; P=0.006) and plasma antioxidant concentrations were significantly lower [vitamin A, 39.5 ± 14.1 vs. 52.4±16.2 μg/dL, respectively (P=0.0004); vitamin E, 8.29±2.1 vs. 9.89±4.5 μg/mL (P=0.043); zinc, 0.61±0.14 vs. 0.67±0.15 mg/L (P=0.016)] in the HIV/HCV‐coinfected participants than in the HIV‐monoinfected participants, and these differences remained significant after adjusting for age, gender, CD4 cell count, HIV viral load, injecting drug use and race. There were no significant differences in glutathione peroxidase concentration, selenium concentration, body mass index (BMI), alcohol use or tobacco use between groups. Glutathione peroxidase concentration significantly increased as liver disease advanced, as measured by APRI (β=0.00118; P=0.0082) and FIB‐4 (β=0.0029; P=0.0177). Vitamin A concentration significantly decreased (β=?0.00581; P=0.0417) as APRI increased.

Conclusion

HIV/HCV coinfection is associated with increased oxidative stress and decreased plasma antioxidant concentrations compared with HIV monoinfection. Research is needed to determine whether antioxidant supplementation delays liver disease in HIV/HCV coinfection.

     

Children''s Asthma, Internalizing Problems, and Social Functioning: An Urban Perspective

PROBLEM: Asthma may serve as a risk factor for higher levels of psychosocial problems in urban school-aged children. METHOD: Interview data were collected from 48 children (27 with asthma and 21 without asthma) and their mothers. FINDINGS: Asthma did not function as a risk factor for psychosocial problems in this sample. Children with more symptoms of depression and anxiety experienced poorer social functioning, regardless of their health status. CONCLUSION: These results highlight the importance of examining co-occurring difficulties in psychosocial development among urban children in order to design interventions that minimize the impact of such challenges.     

肝硬变和肝细胞癌组织中CD54,CD80,CD86和HLA-ABC的表达

目的探讨CD54,CD80,CD86和HLA-ABC在肝硬变的免疫损伤和抗肝癌免疫中的意义.方法用免疫组化方法检测CD54,CD80,CD86和HLA-ABC在肝硬变(n=30)和肝癌(n=48)中的表达、定位和分布.结果在LC中,CD54阳性率为40%(12/30),CD80为50%(15/30),CD86为37%(11/30),HLA-ABC为63%(19/30);在HCC中,CD54阳性率为77%(37/48),CD80为19%(9/47),CD86为13%(6/47),HLA-ABC为30%(12/40);在癌周围组织(PCT)中,CD54为阴性,CD80阳性率为44%(14/32),CD86为47%(15/32),HLA-ABC为53%(17/32).统计学处理显示,在LC中,CD54阳性率显著低于HCC(P＜0.01);CD80(P＜0.01),CD86(P＜0.05)和HLA-ABC(P＜0.01)均显著高于HCC;而与PCT无显著差别.在HCC中,CD80(P＜0.05),CD86(P＜0.01),HLA-ABC(P＜0.05),均显著低于PCT.结论 CD54,CD80,CD86和HLA-ABC在LC和HCC中的同时足量表达有可能引起肝细胞损伤和有效抗肿瘤免疫应答,而CD80,CD86表达的缺失或不足可能是HCC产生免疫逃避的主要原因.     

Clinical and echocardiographic survey of the Ehlers-Danlos syndrome

Cardiac abnormalities such as mitral valve prolapse (MVP) are reported to be common features of the Ehlers Danlos syndrome (EDS), and it has been suggested that the majority of patients with type IV EDS will have cardiac involvement and vascular aneurysms. However, the evidence for valve lesions is inconsistent and often based on early clinical studies using mainly M-mode echo. We studied 33 patients (six male, 27 female; median age 35 yr) with EDS (30 type I, II or III, three type IV) and 30 age- and sex-matched controls. The study assessed skin stretch and joint hypermobility using Beighton and Contompasis scores. Echocardiographic examination included standard two-dimensional views from the parasternal and apical windows, and measurement of the aorta at four sites (annulus, sinotubular junction, arch and abdominal aorta). Echocardiographic abnormalities were found in four patients (12.1%) (one atrial septal aneurysm, one tricuspid prolapse, two MVP) and two controls (6.7%). MVP was found in 6.1% of EDS patients and 7% of controls. Seven patients had previously been diagnosed as having MVP; only two were shown to have true MVP using current criteria. None of those with type IV EDS had any echocardiographic abnormality. No patients with EDS had mean aortic dimensions outside the normal range at any of the points tested. Cardiac symptoms were more frequent amongst the patients than controls (atypical chest pain 48%, P = 0.0001; palpitation 39%, P = 0.001; exertional dyspnoea 30%). A wide range of rheumatological complaints were reported (current arthralgia 75%; recent back pain 72%, P = 0.005; recurrent dislocation 72%). Contrary to earlier published observations, we have not found an increased incidence of cardiac abnormalities in EDS. This syndrome may be relatively more benign, from the cardiac point of view, than was previously thought.      

Video capsule endoscopy for previous overt obscure gastrointestinal bleeding in patients using anti‐thrombotic drugs

Background and Aim: Little is known about the causes of overt obscure gastrointestinal bleeding (OGIB) in patients using anti‐thrombotic therapy. We aimed to describe video capsule endoscopy (VCE) findings and to identify factors associated with positive findings in these patients. Methods: We carried out a retrospective study of 56 patients who underwent VCE for evaluation of previous overt OGIB during anti‐thrombotic therapy. VCE studies were re‐evaluated by a gastroenterologist blinded to clinical details. Clinical data included in the multivariate analysis were sex, age, indication for and type of anti‐thrombotic therapy, hemodynamic instability on admission, type of blood loss, hemoglobin on admission, use of a proton pump inhibitor, NSAID use, time between bleeding episodes and VCE, and whether or not anti‐thrombotic therapy was resumed before the VCE study. Results: A probable cause for gastrointestinal bleeding was identified in 28 (50%) of the 56 studies. Angiodysplasia was found in 19 patients. Twenty‐two studies showed a possible cause in the small bowel. Multivariate logistic regression analysis showed that reinstitution of anti‐thrombotic therapy before VCE was carried out was the only independent predictor of positive VCE findings (OR: 8.61, 95% CI: 1.20–60.42, P = 0.032). Conclusions: Small intestinal angiodysplasia was the most common cause for overt OGIB. Reinstitution of withdrawn anti‐thrombotic drugs before the VCE examination was carried out was associated with positive VCE findings in multivariate analysis.     

The role of torovirus in nosocomial viral gastroenteritis at a large tertiary pediatric centre

OBJECTIVE:

To describe the viral etiology and epidemiology of nosocomial viral gastroenteritis (NVG) at a tertiary care pediatric hospital and identify any changes over the past two decades.

METHODS:

Retrospective review of all patients with laboratory-confirmed NVG at The Hospital for Sick Children (Toronto, Ontario), from January 1, 2004, to December 31, 2005.

RESULTS:

One hundred forty-two episodes of NVG were found among 133 patients, occurring in 0.48 of 100 admissions. The median age was two years; 42% were <1 year of age and 41% were immunocompromised. The most commonly detected pathogen was torovirus (67% of episodes), followed by rotavirus (19%) and adenovirus (9%). Seventy-five cases (53%) were epidemiologically linked in 32 separate clusters (median cluster size two, range two to four). The NVG rate fell from 0.63 of 100 to 0.22 of 100 admissions after March 2005 (P<0.001) when enhanced infection control precautions were instituted in response to an outbreak of vancomycin-resistant Enterococcus.

CONCLUSIONS:

Torovirus remains the most commonly identified cause of NVG at The Hospital for Sick Children. Most NVG cases were epidemiologically linked, and a significant reduction in cases occurred after the institution of enhanced infection control practices following an outbreak of vancomycin-resistant Enterococcus. Improved education and surveillance for NVG should lead to further reduction in this problem.     

Partial plasma exchange using albumin replacement: removal and recovery of normal plasma constituents

Using albumin and crystalloid as the only replacement fluids, the effect of partial plasma exchange on the removal and recovery of normal plasma constituents was studied. The results of 30 procedures on 10 individuals were evaluated. Four patterns of removal are described: reduction in the concentration of fibrinogen and C3 were greater than would be expected based upon the extent of the exchange, while IgG, IgM, cholesterol, alkaline phosphatase and SGPT were removed as expected. Reduction of serum glutamicoxalacetic transaminase (SGOT), lactate dehydrogenase (LDH), amylase, and creatine phosphokinase (CPK) averaged 17% less, and uric acid, calcium and K+ averaged 53% less than expected. Concentrations of HCO-3 and glucose did not change. The mean recovery for all constituents except fibrinogen, C3, cholesterol. IgG and IgM was near 100% at 48-72 hr postpheresis. The 72-hr recovery of fibrinogen and complement was 66% and 60%, respectively. Cholesterol recovery was also slow, requiring a minimum of 1 wk to reach prepheresis levels. Measured at a time when quantitative IgM levels were still reduced, alloantibody agglutinating activity (anti-A and anti-B) in a postpheresis sample exceeded prepheresis agglutinating activity. These data demonstrated that, depending upon quantity and frequency of pheresis, partial plasma exchange using albumin replacement may cause progressive marked reduction in concentrations of immunoglobulin, complement, fibrinogen, and cholesterol. Furthermore, newly synthesized antibody may have increased biologic activity.