Randomized controlled trial on immunomodulatory effects of azithromycin in children with steroid-dependent nephrotic syndrome.

BACKGROUND: Azithromycin (AZM) is a macrolide antibiotic with anti-inflammatory and immunomodulatory effects. Our aim was to compare the immunomodulatory effects of AZM combined with steroid therapy with that of steroid therapy alone in children with steroid-dependent nephrotic syndrome (SDNS). METHODS: We enrolled 57 patients with SDNS in a multicenter randomized control trial. Patients were classified into two groups: group A (intervention group, N = 29) and group B (control group, N = 28). After achievement of remission with full-dose daily prednisone, patients in group A received AZM in conjunction with steroids which was tapered gradually, while patients in group B received steroids alone. Urine protein creatinine ratio (uPCR) and TNF-α were measured at different points of follow-up throughout the study period (5 months after achieving remission). RESULTS: After achievement of remission by full-dose steroids, there were significant differences of TNF-α between the two groups after 1-, 3- and 5-month follow-up (p < 0.001, 0.003, and 0.001, respectively). Also, there was significant difference of TNF-α in both intervention and control groups after exclusion of the relapsed cases at 3- and 5-month follow-up (, p = 0.031 and p = 0.003, respectively). There was significant difference between both groups after 5-month follow-up as regards the number of relapsed patients (group A = 4, group B = 11, p = 0.015). CONCLUSION: AZM was capable of reducing serum TNF-α which is one of the inflammatory cytokines implicated in the pathogenesis of NS.

Ketorolac-fluconazole: A New Combination Reverting Resistance in Candida albicans from Acute Myeloid Leukemia Patients on Induction Chemotherapy: In vitro Study.

BACKGROUND AND OBJECTIVES: Candida albicans is a significant source of morbidity and mortality for patients with acute myeloid leukemia (AML). Prolonged use of fluconazole as empirical antifungal prophylaxis in AML patients leads to overexpression of efflux pump genes that resulted in the emergence of azole-resistant species. Consequently, the introduction of a new strategy to improve the management of C. albicans infections is an urgent need. Nonsteroidal anti-inflammatory drug (NSAID) ketorolac is associated with a reduction in cancer relapses. The present study was performed to investigate the use of ketorolac-fluconazole combination to reverse fluconazole resistance in C. albicans isolated from AML patients on induction chemotherapy. PATIENTS AND METHODS: One hundred and seventy AML patients were evaluated. Fifty C. albicans were isolated and subjected to disc diffusion assay and broth microdilution for fluconazole alone and combined with different concentrations of ketorolac. Efflux pump gene (CDR1, CDR2, and MDR1) expressions were quantified by real-time PCR. RESULTS: The tested ketorolac acted synergistically with fluconazole against resistant C. albicans with the minimum inhibitory concentration (MIC) of fluconazole decreased from >160 µg/mL to 0.3-1.25 µg/mL in (93.8%) of resistant isolates with fractional inhibitory concentration index (FICI) value of 0.25. The majority of the resistant isolates overexpressed CDR1 (71.1%) and MDR1 (60%). CONCLUSION: Ketorolac-fluconazole in vitro combination would be a promising strategy for further clinical in vivo trials to overcome fluconazole resistance in AML patients on induction chemotherapy.

Evaluation of Serum IFN- and IL-5 Levels in Response to Entecavir Therapy in Patients with Chronic Hepatitis B Virus Infection.

Current treatment guidelines recommend the use of entecavir (ETV) as a first-line therapy for chronic HBV infection. Still little is known about its role in restoration of the exhausted HBV immune response. The aim of our study was to assess HBeAg serologic response and serum levels of IFN-γ and IL-5 before and after one year treatment with ETV in chronic hepatitis B patients (CHB) in a trial to find possible predictors for response to ETV treatment in those patients (hepatits B viral clearance and HBeAg seroconversion). The study included 30 chronic hepatitis B patients. All patients received de novo entecavir monotherapy at a daily dose of 0.5 mg for 1 year. Virologic [HBV DNA load, HBV markers (HBsAg, HBeAg, HBeAb)], Biochemical (AST and ALT) and immunological (serum IFN- and IL-5) assessments were done for all patients before and a year after treatment in comparison with healthy controls. Levels of AST and ALT were significantly reduced in all treated patients and normalized in 15. HBeAg seroconversion was achieved in 17 patients, HBV DNA was markedly decreased in all patients and not detectable in 10 of them. IFN-  level increased and IL-5 levels decreased markedly reaching normal levels. Significant relations were detected between HBV DNA, IL-5, HBeAg seroconversion and virologic response (VR) to ETV. ROC curve analysis have shown good prognostic accuracy for both pretreatment HBV DNA and IL5 levels in predicting VR and HBeAg seroconversion after ETV therapy in CHB patients, with pretreatment HBV DNA having somewhat better accuracy and higher propability for the test being correct in predicting loss of HBeAg after treatment. In conclusions, ETV markedly reduced HBV DNA and ALT levels, restored IFN- and IL-5 normal levels and HBeAg seroconversion was achieved in some patients. Both pretreatment levels of HBV DNA and IL5 can be used in predicting VR to ETV but HBV DNA is superior in predicting HBV seroconversion in HBeAg positive patients.

Correction to: Genetic aberrations of the K-ras proto-oncogene in bladder cancer in relation to pesticide exposure.

The original publication of this paper contains a mistake. Line 6 in the abstract, line should read "One hundred patients were diagnosed with bladder cancer and two hundred controls attended the outpatient clinic;"

Bloodstream Infections in Febrile Neutropenic Pediatric Cancer Patients: Microbiological and Sepsis Biomarkers Insight.

The diagnosis of blood steam infections (BSIs) in febrile neutropenic pediatric cancer patients (FNPCP) remains a challenge. Although blood culture is the most accurate method; yet the delay in results has urged the need for reliable biomarkers for early diagnosis. The objectives of this study were to identify the bacterial causes of BSIs in FNPCP at SECI and their antimicrobial susceptibility patterns. Also, to assess the value of procalcitonin (PCT), interleukin 6 (IL6), and interleukin 10 (IL 10) for early diagnosis of BSIs. This study included 68 FNPCP with a total of 85 fever episodes. Blood cultures were done at the onset of fever. Identification of the organisms was carried by Vitek 2 system and the antimicrobial susceptibility testing by disc diffusion. The levels of PCT, IL-6 and IL-10 serum levels were measured by ELISA. Blood stream bacterial infection was detected in 29.4% (25/85). Most were Gram positive cocci in 53.6 % (15/28). There were high percentages of multidrug resistant organism (MDRO) (73.3% and 92.3% among Gram positive and negative bacteria, respectively). The least percentage of resistance was to linezolid (0%) and amikacin (15.4%). The levels of the biomarkers were significantly higher in patients with positive bacterial cultures compared to those with negative cultures (P < 0.001). IL -6 had the best sensitivity (96%) (AUC 0.975, cut off 0.925ng/L) with considerable specificity (88.3%). Combined PCT & IL-6 had the highest sensitivity (96%) and specificity (98.3%). We conclude that the percentage of BSIs among FNPCP was considerable. Gram positive bacteria were the commonest causes. High percentages of MDRO were reported. The most efficient antimicrobials were linezolid and amikacin. IL-6 alone had the best sensitivity for early diagnosis of BSIs. The combination of PCT and IL 6 showed the best performance.

Genetic aberrations of the K-ras proto-oncogene in bladder cancer in relation to pesticide exposure.

In Egypt, bladder cancer is one of the most popular cancers, accounting for 31% of all cancer cases. It ranks first in males about 16.2% of male cancer. The incidence in rural areas among males is near 32 per 100,000. The exact etiology of bladder cancer is still unknown; K-ras gene is known as a critical DNA target for chemical carcinogens such as pesticide. Some occupational hazard exposure is thought to be directly genotoxic, while others might enhance the mutagenicity and carcinogenicity of directly acting genotoxic agents. Analysis of the relationship between pesticide exposure and mutation in the K-ras gene in human bladder cancer. One hundred patients were diagnosed with bladder cancer and two hundred controls attended the outpatient clinic; after taking consent and filling a questionnaire for age, sex, occupation and pesticide exposure, surgically resected specimens were collected and the samples were used to determine the k-ras mutation. Blood samples were taken to analyze the level of acetylcholinesterase enzyme and level of P53. The present study indicated that pesticide exposure may play a great role in malignant transformation of the bladder cells through mutation in the K-ras gene; there was a significant correlation between the acetylcholinesterase enzyme level and k-ras mutation (p < 0.001). The results revealed that the level of P53 was significantly high in comparison with the control group (p < 0.001). These findings give an alarm to decrease the amount of pesticides used in our area; also, p53 may be used as an indicator to bladder cancer.

Prevalence of Occult HBV Infection Among Chronic Hepatitis C Patients in Upper Egypt.

Occult hepatitis B virusinfection (OBI) is defined as the presence of HBV DNA in liver or serum of individuals who test negative for hepatitis B surface antigen (HBsAg).We aimed at determining the prevalence of OBI in patients chronically infected with HCV in Upper Egypt and to evaluate the possible impact of OBI on the progression of the liver disease. This study included 200 chronic HCV infected patients. HBV DNA was detected in the serum of 21 patients (10.5%) by nested PCR. 13 of them were positive for anti-HBc. HBV viral load ranged from 4.2-60.1 IU/ml. The percentage of cirrhotics was higher among OBI/HCV dual infection (52.4%) versus HCV mono infection (34.1%). Our study concluded that the prevalence of OBI among chronic HCV patients in Upper Egypt was 10.5%. OBI correlated with the severity of liver disease. Total anti-HBc cannot be used as a surrogate marker for detection of OBI.

Patterns of Candida biofilm on intrauterine devices.

Biofilms are colonies of microbial cells encased in a self-produced organic polymeric matrix and represent a common mode of microbial growth. Microbes growing as biofilm are highly resistant to commonly used antimicrobial drugs. We aimed to screen and characterize biofilm formation by different isolates of Candida on removed intrauterine devices (IUDs), to perform experimental biofilm formation with isolated strains, and to examine biofilm by the crystal violet and XTT reduction assays and scanning electron microscopy (SEM). A total of 56 IUDs were examined for biofilm formation using Sabouraud's dextrose chloramphenicol agar. Suspected colonies were identified by different methods. Antifungal susceptibility testing with fluconazole (FLU) and amphotericin B for the isolated strains and in vitro experimental biofilm formation was carried out. The biofilm was quantified by crystal violet, XTT reduction assay and SEM. Among the 56 IUDs investigated, 26 were Candida positive (46.4 %). Candida albicans was recovered from 15 isolates. The biofilm MIC of FLU was increased 64 to 1000 times compared to the MIC for planktonic cells. The XTT method results were dependent on the Candida species; biofilm formation was highest in Candida krusei and Candida glabrata strains, followed by C. albicans and Candida tropicalis. SEM of Candida biofilm revealed a heterogeneous thick biofilm with a mixture of micro-organisms. The main conclusion from this study was non-albicans Candida represents more than a half of the Candida biofilm. Better understanding of Candida biofilms may lead to the development of novel therapeutic approaches for the treatment of fungal infections, especially resistant ones among IUD users.

Pattern of hepatitis virus infection among pregnant women and their newborns at the Women's Health Center of Assiut University, Upper Egypt.

OBJECTIVE: To determine the prevalence, risk factors, and rate of vertical transmission of HBV and/or HCV infection among pregnant women in Upper Egypt, and assess the preventive efficacy of administering hepatitis B immunoglobulin and vaccine to newborns on their carrier status at 8 months. METHODS: Five hundred pregnant women were screened for HCV and HBV serum markers by enzyme-linked immunoassay. Those testing positive had their status confirmed by polymerase chain reaction and their levels of liver enzymes and interferon gamma were evaluated. The newborns of HBV-positive women received hepatitis B immunoglobulin and vaccine and were followed up to assess the rates of vertical transmission and carrier status among the newborns. RESULTS: Of the 500 pregnant women, 6.4% were HCV positive, 4.0% were HBV positive, and 1.0% were both. The vertical transmission rate was 3.1% for HCV, 30.0% for HBV, and 20.0% for a combined infection. The carrier rate of the infants at the end of their eighth month was 10.8% for those with HCV and 8% for those with HBV. CONCLUSION: Infection with HBV and/or HCV is highly prevalent among pregnant women in Upper Egypt. The rate of vertical transmission was also high. Administering hepatitis B vaccine and immunoglobulin resulted in a 92% reduction in carrier status among newborns.