Nga Hin Pong

Thrombopoietin Protects Against In Vitro and In Vivo Cardiotoxicity Induced by Doxorubicin

Background— Doxorubicin (DOX) is an important antineoplastic agent. However, the associated cardiotoxicity, possibly mediated by the production of reactive oxygen species, has remained a significant and dose-limiting clinical problem. Our hypothesis is that the hematopoietic/megakaryocytopoietic growth factor thrombopoietin (TPO) protects against DOX-induced cardiotoxicity and might involve antiapoptotic mechanism exerted on cardiomyocytes. Methods and Results— In vitro investigations on H9C2 cell line and spontaneously beating cells of primary, neonatal rat ventricle, as well as an in vivo study in a mouse model of DOX-induced acute cardiomyopathy, were performed. Our results showed that pretreatment with TPO significantly increased viability of DOX-injured H9C2 cells and beating rates of neonatal myocytes, with effects similar to those of dexrazoxane, a clinically approved cardiac protective agent. TPO ameliorated DOX-induced apoptosis of H9C2 cells as demonstrated by assays of annexin V, active caspase-3, and mitochondrial membrane potential. In the mouse model, administration of TPO (12.5 &mgr;g/kg IP for 3 alternate days) significantly reduced DOX-induced (20 mg/kg) cardiotoxicity, including low blood cell count, cardiomyocyte lesions (apoptosis, vacuolization, and myofibrillar loss), and animal mortality. Using Doppler echocardiography, we observed increased heart rate, fractional shortening, and cardiac output in animals pretreated with TPO compared with those receiving DOX alone. Conclusions— These data have provided the first evidence that TPO is a protective agent against DOX-induced cardiac injury. We propose to further explore an integrated program, incorporating TPO with other protocols, for treatment of DOX-induced cardiotoxicity and other forms of cardiomyopathy.

Efficacy of sodium hypochlorite (bleach) baths to reduce Staphylococcus aureus colonization in childhood onset moderate-to-severe eczema: A randomized, placebo-controlled cross-over trial

Abstract Background: Staphylococcus aureus (S. aureus) colonization/infection is an important factor in the pathophysiology of atopic dermatitis (AD). Clinical trials have demonstrated conflicting efficacy of diluted bleach baths in treating moderate-to-severe AD. We conducted a double-blinded, placebo-controlled (water), cross-over trial among patients with AD to investigate the efficacy of bleach baths in reducing S. aureus colonization and AD severity. Method: In this cross-over trial, 40 patients with moderate-to-severe AD were randomized to receive twice-weekly bleach and water baths, each for four consecutive weeks with a four-week wash-out period in between. Condition of S. aureus growth and SCORing Atopic Dermatitis index (SCORAD) were recorded at baseline and four-weekly intervals. Patients’ blood was collected in first and second visits to investigate blood eosinophil count, serum levels of total IgE and specific IgEs against Staphylococcal enterotoxins A and B. In every visit, Children Dermatology Life Quality Index (CDLQI), skin hydration (SH), transepidermal water loss (TEWL) and usage frequency of prohibited medications (topical antibiotic, steroid and oral antihistamine) were recorded. Results: All 40 patients completed the trial, but 14 were non-adherent. By intention-to-treat (ITT) approach, comparing with water baths, bleach baths conferred no significant efficacy in CDLQI, SH, TEWL, blood eosinophil count, total IgE and the two specific IgEs over four weeks. Water baths caused a greater reduction in affected area of SCORAD than bleach baths (−5.7 ± 15.4 for water vs. 0.6 ± 12.4 for bleach; p = 0.03) by ITT, and in objective SCORAD and affected area (p < 0.05) from per-protocol approach. Bleach baths reduced topical corticosteroid use (mean difference = 1.1 ± 2.6 days/week; p = 0.014) and topical antibiotic use (mean difference = 1.0 ± 2.8 days/week; p = 0.044) in within-group analysis. Conclusions: This study demonstrated that a four-week, twice-weekly regime of diluted bleach baths is not more useful than water baths in reducing S. aureus colonization/infection and improving AD. A longer treatment period is needed to evaluate if the short treatment duration was the main cause for the discrepancy in outcome from other bleach-bath trials. The usage of a portable bath tub obviates the problems associated with unavailability of bathing facilities in some families.

Quality of life and psychosocial issues are important outcome measures in eczema treatment

Abstract Background: Atopic eczema (AE) is a common relapsing inflammatory skin disease in children associated with chronicity and poor quality of life. Many children also display depressive, anxiety and stress symptoms. Aim: To investigate the prevalence of depressive, anxiety and stress symptoms, and if these symptoms are associated with disease severity, quality of life and skin biophysiology in childhood AE. Methods: Psychological symptoms, eczema severity, quality of life and biophysical skin condition of consecutive adolescents at the pediatric dermatology clinic of a teaching hospital were evaluated with the validated Chinese versions of Depressive, Anxiety, Stress Scales (DASS-42), Beck Depression Inventory (BDI-13), Nottingham Eczema Severity Score (NESS), Children’s Dermatology Life Quality Index (CDLQI), transepidermal water loss (TEWL) and stratum corneum skin hydration (SH), respectively. Results: AE patients (n = 120) had lower SH, higher TEWL, worse CDLQI and reported higher overall, depressive and stress symptom scores, personal history of atopy, current topical corticosteroid usage and food avoidance than non-AE patients (n = 26). Depressive, anxiety and stress symptoms were reported in 21%, 33% and 23% of AE patients, respectively. Multivariate analyses showed that these symptoms were significantly correlated with a poor quality of life (partial correlations of 0.40–0.49; p < 0.001). Male patients had more severe disease (higher NESS, p = 0.036) and DASS-depressive symptoms (multivariate OR = 3.2, p = 0.034) than females. Patients who reported current topical steroid usage generally practiced food avoidance (p = 0.047), had poor quality of life (p = 0.043) but less DASS-depression (multivariate OR = 0.354, p = 0.043). Only 6% of the 120 AE patients reported prior psychology consultation. Conclusions: Quality of life impairments correlate with disease severity, aberrant skin biophysiology, depression, anxiety and stress symptoms in adolescents with AE. Physicians caring for these patients must evaluate the different but inter-correlated medical, biophysiological and pertinent psychosocial domains. These significant correlations imply that a holistic approach should encompass psychotherapy, behavioral therapy and coping strategies in conjunction with dermatologic therapy.

Correlations among steroid fear, acceptability, usage frequency, quality of life and disease severity in childhood eczema

Abstract Topical corticosteroids (CSs) are the mainstay of treatment for eczema but CS phobia and fears are prevalent and influence therapeutic efficacy. Aim: To quantify if CS acceptability and fear affect patients’ quality-of-life (QoL). Methods: Patients with eczema managed in the pediatric dermatology outpatient clinic of a university hospital were surveyed. Nottingham Eczema Severity Score (NESS) for severity, Children’s Dermatology Life Quality Index (CDLQI) for QoL, CS fear, acceptability and reported frequency of CS use were measured with quantified questions. Results: CS fears were prevalent among parents and caregivers of patients with eczema. Fifty-eight percent of parents reported general acceptability of CS as being very good or good, and many applied CS to their child regularly every week. However, >40% of parents reported CS fear “always” or “often”, 41% reported that they “always” or “often” apply CS only when eczema got worse, 57% would discuss CS fear with their doctors, 30% would request CS-sparing medications and 14% “always” or “often” use traditional Chinese herbal medicine. Fears were predominantly interpersonal and less often iatrogenic in nature. Skin problems were the most concerned side effects of CS. CS acceptability, frequency of CS usage, CS fear and usage of alternative medications were independent domains in eczema management: CS fears correlated with CDLQI; CS usage frequency correlated with NESS and negatively with parental education; and CS acceptability correlated with parental education. Ordinal logistic regressions showed worse QoL was associated with more CS fear (odds ratio: 1.092 [95% CI: 1.023–1.165], p = 0.008). Conclusions: The extent of CS fears is independent of CS acceptability, but correlates with patients’ QoL. Desensitization of parental CS fears should be integral part of eczema education and therapeutics in order to improve therapeutic efficacy and patients’ QoL.

The ideal moisturizer: a survey of parental expectations and practice in childhood-onset eczema

Abstract Aim: We evaluated the moisturizing and bathing practices and preferences of patients with childhood-onset eczema. Methods: The attitudes and practice of patients with eczema managed at a pediatric dermatology clinic were evaluated, using children with non-eczematous skin diseases as controls. Disease severity of eczema in the preceding 12 months was evaluated by the Nottingham Eczema Severity Score (NESS). Skin hydration (SH) and transepidermal water loss (TEWL) were assessed. Results: Majority of patients took shower instead of bath and spent 12–13 min in shower. Most eczema patients applied emollients after shower/bath. Air-conditioning use was frequent, and patients with eczema maintained a lower ambient temperature than non-eczema patients (p = 0.001). Most eczema patients reported regular emollient usage (1.8 times/day for mild vs 2.8 times/day for moderate-to-severe eczema, p = 0.001), and acceptability of the current product was good to fair. Parents reported that the current emollients were most often recommended by doctors. Majority of parents/patients with mild eczema thought an ideal emollient needs only to be used twice a day whereas moderate-to-severe patients preferred more frequent usage (p = 0.001), and most of them preferred a non-fragrant, non-herbal white cream. Agreements concerning ideal emollient usage were only “moderate-to-fair” (kappa values <0.61), implying what parents/patients practiced was not the same as what they preferred. Conclusion: This study helps better understand the emolliation practices and preferences of eczema patients. Doctors remain the most important source of recommendation. Majority think an ideal moisturizer is a non-fragrant, non-herbal, white or transparent cream which needs only to be used two to three times per day. Compliance may be enhanced if the recommended moisturizer conforms to the parents/patients preference.

Clinical features and Staphylococcus aureus colonization/infection in childhood atopic dermatitis

Abstract Introduction: Staphylococcus aureus (SA) colonization/infection is important in the pathophysiology of childhood atopic dermatitis (AD). This study evaluated which clinical features may predict presence of SA colonization/infection and reviewed antimicrobial sensitivity of SA in patients with AD. Methods: The associations between bacteriologic culture results of skin swabs (taken at the most severely affected area and at the antecubital fossa) and SCORing-Atopic-Dermatitis (SCORAD), skin hydration, transepidermal water loss (TEWL), and quality of life were evaluated. Results: Moderate-to-heavy growth of SA was present in 31% of the swabs of the most severe area and in 16% of the flexural (antecubital fossae) areas of 95 AD patients (12.5 ± 4.8 years). Binomial logistic regression showed moderate-to-heavy growth of SA in the severe area were associated with objective SCORAD (p = 0.004) and lesion intensity [erythema (p = 0.022) and lichenification (p = 0.035)]; and excoriation (p = 0.024) and TEWL (p = 0.009) in the antecubital fossa. The relative risk of isolating moderate-to-heavy growth of SA in the most affected area in patients with severe disease (objective SCORAD >40) is 2.73 (1.43–5.21, p = 0.001). Any growth of SA in either swab sites was associated with objective SCORAD and lesion intensity (p = 0.001–0.019). SA had no association with quality of life and other clinical parameters. All specimens of methicillin-sensitive SA were sensitive to cloxacillin. All methicillin-resistant SA (MRSA) (5.7%) was sensitive to co-trimoxazole and fusidic acid. Conclusions: Clinical features, especially severity and lesion intensity, are useful in “predicting” moderate-to-heavy SA colonization/infection in AD patients. Cloxacillin has a favorable sensitivity profile for MSSA, and co-trimoxazole and fusidic acid for MRSA. As colonization and infection are ambiguous and potentially overlapping clinical states, we recommend to abandon these terms and propose to describe quantitatively/semi-quantitatively SA isolation as none, mild, scanty, moderate or heavy growth instead in clinical trials.

Cardioprotective effect of dexrazoxane in a rat model of myocardial infarction: Anti-apoptosis and promoting angiogenesis

OBJECTIVES Dexrazoxane (DZR) is a clinically approved agent for preventive treatment of doxorubicin-induced cardiotoxicity. The objective of this study was to investigate the cardioprotective effects of DZR in a rat model of myocardial infarction (MI). METHODS Sprague-Dawley rats were randomly divided into four groups: MI (n = 16), MI + DZR (n = 16), SHAM-operated (n = 14) and DZR-only (n = 9). MI animals were subjected to left anterior descending coronary artery ligation. DZR was administered as a single dose at 125 mg/kg intraperitoneally. Four weeks after treatment, cardiac function by echocardiography, infarct size, capillary density in the infarct border zone, bone marrow-derived endothelial progenitor cells (EPCs), and cardiac expression of Bax were measured. RESULTS Our results demonstrated that MI animals had compromised heart parameters. DZR treatment in MI animals resulted in reduction in infarct size (P = 0.013) and improved cardiac functions in terms of fractional shortening (P = 0.004) and ejection fraction (P = 0.004). The capillary density (P = 0.008) and bone marrow-derived EPCs (P < 0.05) were higher in the MI + DZR group than those in the untreated MI group. Bax expression was down-regulated in heart tissues of MI + DZR animals (P = 0.043). CONCLUSIONS Our study demonstrated that DZR exerted a cardioprotective effect in the rat model of MI, and the mechanism might be associated with anti-apoptosis and increased neovascularization.

Exploring Staphylococcus epidermidis in atopic eczema: friend or foe?

Staphylococcus aureus (SA) colonization/infection is important in the pathophysiology of childhood atopic dermatitis (AD), but the role of Staphylococcus epidermidis (SE) is unknown.

Circulating Immunoglobulins, Leucocytes and Complements in Childhood-onset Atopic Eczema

ObjectiveTo evaluate if eczema severity is associated with blood levels of immunoglobulins, white cell differentials and complements.MethodsWhite cell differentials, levels of serum immunoglobulins and complements of patients with eczema and miscellaneous non-eczema skin diseases were measured. Eczema severity and quality of life were assessed by SCORAD, Nottingham Eczema Severity Score (NESS) and Children’s Dermatology Life Quality Index (CDLQI). Correlations were analyzed by Pearson’s correlation test for parametric data and Spearman’s rho correlation test for non-parametric data.ResultsSerum IgE and peripheral blood eosinophil percentage were significantly higher in patients with eczema than other non-eczema skin diseases. Levels of IgE (log-transformed), IgA and IgG correlated with objective SCORAD (r = 0.52, 0.40, 0.29, respectively). Levels of eosinophil, neutrophils, lymphocytes and complements also correlated with objective SCORAD, with the eosinohil/lymphocyte ratio showing the highest correlation (r = 0.60, p < 0.01). Ratios of IgE/IgA, IgE/IgG, eosinophils/lymphocytes, eosinophils/neutrophils correlated positively with CDLQI. IgM appeared to have no correlation with eczema.ConclusionsBlood levels of IgE, IgA, IgG,eosinophils, lymphocytes, neutrophils and complements pathophysiologically correlate with eczema severity. Eosinophil/lymphocyte ratio may represent a readily-available objective laboratory correlate of eczema severity. Eczema is a complex atopic disease involving many cellular and humoral components of the immune system.

Specific IgG and IgA of common foods in Chinese children with eczema: Friend or foe

Abstract Background: Specific immunoglobulins G and A (IgG and IgA) for common food items have been extensively measured as surrogate markers of food allergy, and dietary avoidance based on the test results advocated. Aim: We reviewed the prevalence of specific food IgG and IgA in children with eczema and evaluated outcome of dietary avoidance in these children. Methods: Specific immunoglobulins of 96 food items were measured for 30 consecutive atopic dermatitis (AD) patients and disease severity [SCORing atopic dermatitis (SCORAD) and Nottingham eczema severity score (NESS)], Children Dermatology Life Quality Index (CDLQI), skin hydration (SH), transepidermal water loss (TEWL), topical corticosteroid and oral antihistamine usage were evaluated. Twenty seven of these patients received dietary avoidance advice based on IgG and IgA data. General acceptability of treatment (GAT) was documented at the end of 3 months. Results: There were generally no correlations among levels of IgG or IgA of the 96 food items and disease severity, quality of life, SH or TEWL. Two-third patients reported very good or good and one-third reported fair or poor GAT following dietary avoidance advice. There was no difference in any clinical parameters between the two groups following dietary avoidance. Patient with lower sunflower seed IgA (p = 0.043), casein IgG (p = 0.041), milk IgG (p = 0.037) or whey IgG (p = 0.014) had improved SCORAD and objective SCORAD following dietary advice. Conclusion: Children with AD are sensitized to many food allergens via IgG and IgA mechanisms. Levels of food IgG or IgA do not seem to correlate with any clinical parameters in AD. Subjectively, two third of patients accepted dietary manipulations as very good or good for their AD. Objectively, dietary avoidance had few clinical effects on the clinical parameters. Sensitization should not be generalized to mean allergy to common food.