Exacerbation of allopurinol-induced drug reaction with eosinophilia and systemic symptoms by teicoplanin: A case report.

WHAT IS KNOWN AND OBJECTIVE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially life-threatening drug reaction. Allopurinol is one of the most frequently reported drugs accounting for DRESS syndrome development. In contrast to allopurinol, DRESS syndrome induced by teicoplanin has not been reported frequently. CASE DESCRIPTION: A 50-year-old woman was admitted to receive FLAG chemotherapy regimen (fludarabine, cytarabine (high-dose Ara-C), granulocyte colony-stimulating factor) for relapsed acute lymphoblastic leukaemia (ALL) treatment. Allopurinol was initiated at a dose of 300 mg per day 48 hours before chemotherapy regimen initiation, for tumour lysis syndrome prophylaxis. Seven days after allopurinol initiation, the patient presented with fever, dyspnoea, shortening of breath, facial oedema, generalized pruritus, erythema and macular rash affecting the face, abdomen, trunk, upper and lower limbs and an elevation in hepatic enzymes. Allopurinol was immediately discontinued and intravenous hydrocortisone was started concomitantly alongside other supportive measures. About 72 hours later, pruritus, erythema and rash were ameliorated and abnormalities in liver tests were improved. Afterwards, teicoplanin administration led to severe deterioration of pruritus, erythema and rash; subsequently, serum alanine aminotransferase increased again and episodes of worsening dyspnea occurred. Signs of hypersensitivity reaction were reduced by discontinuation of teicoplanin and supportive care. WHAT IS NEW AND CONCLUSION: We report a case of allopurinol-induced DRESS syndrome, which was exacerbated by administration of teicoplanin. It can be suggested that the administration of drugs with high possibility of hypersensitivity reactions should be avoided during the acute phase of DRESS syndrome.

The dilemma of hyperoxia following positive pressure mechanical ventilation: role of iron and the benefit of iron chelation with deferasirox.

BACKGROUND AND OBJECTIVE: Increased oxidative stress in patients under treatment with high concentrations of oxygen (hyperoxia) is considered to be one of the major mechanisms of lung injury, which is thought among different mediators, transition metal ion, iron, by generation of very reactive free radicals which play an important role. Disruption of normal iron homeostasis has been reported in hyperoxic conditions. We hypothesized that chelation of iron can reduce hyperoxia-induced lung injury. METHODS: Mechanically ventilated patients, who received oxygen with FiO2 >0.5 for at least 3 days, underwent bronchoscopy before and 72 hours after receiving "Deferasirox". Oxidative injury index and iron homeostasis markers were measured in lavage fluid and plasma. RESULTS: In 12 patients, the concentrations of 8-isoprostane (p=0.005), 8-oxoguanine (p=0.04), carbonyl proteins (p=0.04)--as markers of oxidative stress--decreased significantly in lavage fluid after intervention. Levels of iron-related proteins, ferritin (p=0.04) and transferrin (p=0.005) also decreased significantly in lavage fluid. CONCLUSION: Deferasirox--as an iron chelator--decrease oxidative injury index in hyperoxic condition and it could be consider safe and beneficial agent, along with other supportive measures in hyperoxia-induced lung injury for better toleration of oxygen therapy.

Evaluation of nutritional status in patients undergoing hematopoietic SCT.

The aims of this study were to establish the nutritional status of patients during hematopoietic SCT (HSCT) and to determine if body mass index (BMI) is a valid indicator of nutritional status in this population when compared with nitrogen balance (NB). In total, 50 patients were enrolled (mean age: 25.7+/-9.0 years). Patients (14%) were underweight (BMI<18.5 kg/m(2)), 58% in a normal BMI (between 18.5 and 24.9 kg/m(2)) and 28% were overweight or obese (BMI >or= 25 kg/m(2)). NB dropped after transplantation and increased from days +5 to +20 after transplantation (P=0.006). There was a significant negative relationship between patients' BMI and time to engraftment (r=-0.45, P=0.001). Engraftment of underweight patients was 3.0 days (P=0.002) and 4.0 days (P<0.001) later than in normal and overweight or obese patients, respectively. There was no significant correlation between NB before transplantation and time to engraftment (r=-0.22, P=0.16). The results of this study demonstrate that patients undergoing HSCT may have suboptimal nutritional status and that pre-HSCT-BMI rather than NB may have a greater correlation in HSCT patients with the time of engraftment. Therefore, it may be useful to consider patient's BMI before transplantation for earlier engraftment time.

Effects of pentoxifylline on oxidative stress and levels of EGF and NO in blood of diabetic type-2 patients; a randomized, double-blind placebo-controlled clinical trial.

BACKGROUND: As oxidative stress contributes to both progression and pathologic complications of diabetes and effective therapeutic strategies to prevent or delay the damage remain limited, the aim of the present study was to assess the efficacy of pentoxifylline in reducing of oxidative stress. Since there is a relationship between nitric oxide (NO), epidermal growth factor (EGF) and oxidative stress, we measured the effect of this drug on these parameters in comparison to placebo. METHODS: Thirty-nine patients with type-2 diabetes mellitus were randomized in a double blind, placebo-controlled clinical trial to receive either pentoxifylline 400 mg four times a day or placebo for 14 days. Blood samples were obtained at baseline and at the end of the study. Samples were analyzed for thiobarbituric reactive substances (TBARS) as a marker of lipid peroxidation, ferric reducing ability (total antioxidant power, TAP), EGF and NO levels. RESULTS: Pentoxifylline in comparison to placebo was effective (P < 0.05) in reduction of lipid peroxidation in plasma of the patients without significant effects on TAP, levels of EGF and NO in plasma. CONCLUSION: Adding of pentoxifylline to drug regimen of diabetic type-2 patients can be helpful. Exact mechanism of action of pentoxifylline in reduction of blood lipid peroxidation remains to be elucidated.

N-acetyl cysteine for prevention of oral mucositis in hematopoietic SCT: a double-blind, randomized, placebo-controlled trial.

Oral mucositis (OM) is a complication of high-dose chemotherapy (HDC) which is frequently observed in hematopoietic SCT settings. Antioxidant agents have been proposed to prevent OM and therefore N-acetyl cysteine (NAC) could have an important role. In the present study, we conducted a double-blind, randomized, placebo-controlled study to evaluate the NAC effect on OM incidence and severity, and also glutathione peroxidase-1 activity. Leukemia patients undergoing allogeneic hematopoietic SCT preceded by HDC were recruited into the study and received either NAC (100 mg/kg/day) (n=38) or placebo (n=42) from the starting day of HDC until day +15 after transplantation. OM was evaluated daily for 21 days after transplantation according to World Health Organization oral toxicity scale. The incidence of severe OM (grades 3-4) was significantly lower in the NAC group (23.7% vs 45.3%, P=0.04). Moreover, the mean duration of OM was significantly shorter in the intervention group (6.24(2.96) vs 8.12(3.97) days, P=0.02). The glutathione peroxidase-1 activity was also significantly higher in the NAC group seven days after transplantation (3.38(2.19) vs 2.41(1.70) ng/mL, P=0.003). It is concluded that parenteral NAC is effective in reducing the incidence of severe cases and the total duration of OM.

The efficacy of selenium in prevention of oral mucositis in patients undergoing hematopoietic SCT: a randomized clinical trial.

Oral mucositis (OM) is a complication of high-dose chemotherapy (HDC) followed by hematopoietic SCT (HSCT) with few effective treatments. Selenium has a cytoprotective role via the glutathione peroxidase (Glu.Px) enzyme and prevents chemotherapy-induced toxicities. We performed a double-blind, randomized, placebo-controlled study to evaluate the efficacy of selenium on the prevention of OM in 77 patients with leukemia, undergoing allogeneic HSCT. Thirty-seven patients received oral selenium tablets (200 mcg twice daily) from the starting day of HDC to 14 days after transplantation. OM was evaluated daily for 21 days after transplantation according to World Health Organization oral toxicity scale. The incidence of severe OM (grades 3-4) was significantly lower in the selenium group (10.8% vs 35.1%, P<0.05). We noted that the duration of objective OM (grades 2-4), excluding patient's self-declaration (grade 1), was significantly shorter in the selenium group (3.6±1.84 vs 5.3±2.2 days, P=0.014). Significant elevations in serum selenium level and plasma Glu.Px activity were observed 7 and 14 days after transplantation compared with baseline in the selenium group. We conclude that selenium can reduce the duration and severity of OM after HDC. Clinicaltrial.org ID: NCT01432873.

Population pharmacokinetics of oral high-dose busulfan in adult patients undergoing hematopoietic stem cell transplantation.

BACKGROUND AND THE PURPOSE OF THE STUDY: Many factors have been reported that contribute to the wide intra- and inter-patient variability of Busulfan (Bu) disposition. The purpose of this study was to develop a population pharmacokinetic model and to determine the covariates affecting the pharmacokinetics (PK) of Bu in Iranian adult patients who received oral high-dose as a conditioning regimen before Hematopoietic Stem Cell Transplantation (HSCT). METHODS: A population PK analysis was performed in 30 patients who received an oral Bu and cyclophosphamide regimen before HSCT. Bu was given orally according to the protocol of the institution. In order to prevent seizures caused by Bu, phenytoin was administered orally one hour before each dose of Bu.A total of 180 blood samples were analyzed by HPLC and PK parameters were estimated by the non-linear mixed effect model by MONOLIX 3.1 program. A one-compartment model with an additive error model was used to describe the concentration-time profile of Bu. RESULTS: Patients' disease and weight was found to be the determinant factors for clearance (CL) and the volume of distribution (Vd) according to Monolix analysis. The covariate entered in final model followed by these equations:[Formula: see text][Formula: see text] In this limited study, the age (15-43 years) had no significant effect. For a patient weighting 60 kg, the typical CL and Vd were estimated to be 13.4 l/hr and 42.6 L, respectively. The interindividual variability of CL and Vd were 13.6 and 6.3%, respectively. There was no significant metabolic induction in these four days as is evident by comparing the trough levels of Bu. However it should be mentioned that, one tailed t-test p-values of the days of two and three, two and four and three and four were 0.083, 0.069 and 0.388, respectively. MAJOR CONCLUSIONS: Results of this study showed that the type of disease was a determinant of CL and the weight of patient was a determinant of Vd for Bu population PK parameters. A reliable PK parameters and Css, estimated from only one plasma concentrations (5 hrs after the first dose), were validated. Since these methods require few sampling and are easy to be used, the limited sampling methods might be advantageous in the routine clinical practice.

Antioxidant properties of peel and pulp hydro extract in ten Persian pomegranate cultivars.

This study compares the antioxidant activity of ten different pomegranate cultivars grown in Iran using the ferric reducing power assay (FRAP assay), which is based on the reduction of a ferric-tripyridyl triazine complex to its ferrous, colored form in the presence of antioxidants. Aqueous solutions of known Fe(+2) concentration, in the range of 100-1000 micromol L(-1) were used for calibration. The results showed that among pulp and peel fractions the sour alac and sweet white peel cultivars had more FRAP value respectively. The pomegranate peel extract had markedly higher antioxidant capacity than the pulp extract. The peel extract of sweet white peel cultivar appeared to have more potential as a health supplement rich in natural antioxidants compared to the pulp and peel extracts of other pomegranate cultivars.