A Pharmacogenetic Study of VDR fok1 and TYMS Polymorphisms and Their Association With Glucocorticoid-Induced Osteonecrosis in Egyptian Children With Acute Lymphoblastic Leukemia

Purpose: Osteonecrosis is a significant toxicity resulting from the treatment of pediatric Acute Lymphoblastic Leukemia (ALL). This study aimed to investigate the relationship between vitamin D receptor fok1 (VDR fok1) and thymidylate synthase (TYMS) gene polymorphisms with the glucocorticoid (GC) induced osteonecrosis (ON) in Egyptian pediatric ALL patients. In addition, to identify the possible association of genetic polymorphisms with other factors such as gender and ALL subtypes.Patients and Methods: A retrospective case-control study was conducted on 102 pediatric ALL patients under the age of 18 who were treated at Children Cancer Hospital Egypt according to St Jude SR/HR total XV protocol. The recruited patients were composed of 51 cases who developed GC-induced osteonecrosis and 51 age- and gender-matched patients who received glucocorticoids but remained osteonecrosis-free (controls). Genotyping of the VDR fok1 and TYMS genes was performed using restriction fragment length polymorphism (RFLP) and conventional PCR, respectively.Results: For the total 102 studied patients, the VDR fok1 single nucleotide polymorphisms (SNPs) frequency distribution were TT (8.8%), CT (34.3%), and CC (56.9%), while the TYMS tandem repeat gene variations were reported as 2R2R (20.6%), 2R3R (45.1%), and 3R3R (34.3%). VDR fok1 and TYMS polymorphic variants showed no association neither with gender; P-values 0.3808 and 0.1503, respectively, nor with ALL subtypes; P-values 0.9396 and 0.6596, respectively. The VDR fok1 polymorphisms showed a significant association with the development of ON; P-value = 0.003, on the other hand, TYMS tandem repeats did not show significant impact on osteonecrosis development; P-value = 0.411.Conclusion: This study showed a significant association between the VDR fok1 polymorphism and osteonecrosis. Such clinical pharmacogenetics results would be promising to discuss the possibility of dose adjustments aiming a regimen with the highest efficacy and least toxicity

Impact of intravitreal injection of Bevacizumab (Avastin) on rabbit′s choroid and retina

AIM: The aim of the study was to evaluate the impact of intravitreal injection of bevacizumab (Avastin) on chorio-capillaris permeability as well as structure changes in the choroid and the retina of pigmented rabbits. MATERIAL AND METHODS: The study included 10 pigmented rabbits (20 clinically free eyes) ranged in weight between 1.2 and 2 kg (mean 1.7±0.05). The rabbits were subjected to intravitreal injection of 5 mg, 0.1mg Avastin in the right eyes (10eyes), while the left eyes (10eyes) were injected with equal volumes of balanced salt solution. 1 week later, Clinical examination and fundus fluorescein angiography (FFA) were done. Histological examination was performed on specimens of retina & choroid of Avastin & BSS injected eyes of sacrificed rabbits using light microscopy (LM) & transmission electron microscopy (TEM). Results were recorded and compared RESULTS: Post injection clinical examination of the eyes showed no abnormality of cornea, lens, vitreous and fundus. FFA showed remarkable decrease in background chorio-capillaris fluorescence in 7 eyes (70 percent) injected with Avastin as compared with eyes injected with BSS. No change was observed in regards to retinal vasculature, or abnormal dye leak. LM examination: specimens from Avastin group were evaluated in comparison to control eyes Treated eyes exhibited the same microscopic appearance in most specimens (8/10, 80 percent). The chorio-capillaris layer showed elongated, stretched monolayer of capillaries with flat, elongated endothelial cell lining. The laminae showed closely packed RBCs arranged in a monolayer with ribbon like shape. The surrounding interstitial tissue showed stretched, elongated & compact collagen fibers. The RPE cells were tightly adherent to each other with prominent nuclei. The different retinal layers were in concomitance with the control specimens, however mild to moderate disruption of photoreceptor outer segments together with mild vacuolization in the ganglion cell layer were seen. TEM examination of both control and treated specimens confirmed the findings recorded by LM. The endothelial cell limning of the choriocapillaris exhibited reduced fenestrations in between the cells. TEM also highlighted the compact lamellae of collagen fibers. The RPE cells showed remarkable increase in the number of mitochondria and prominent endoplasmic reticulum. Variable sized melanosomes were also seen CONCLUSION: Though single intravitreal injection of Avastin does not cause appreciable histological changes in rabbit retina and choroid, yet, it imposes definite effect on choriocapillaris permeability as evidenced by FFA and ultra structural changes. Repeated intravitreal injections might alter the hemostasis of the chorio-capillaris RPE complex

Characterization of pediatric head and neck masses with quantitative analysis of diffusion-weighted imaging and measurement of apparent diffusion coefficients

Purpose: Our objective was to investigate the accuracy of quantitative diffusion-weighted imaging (DWI) to determine the histopathologic diagnosis of pediatric head and neck lesions. Materials and Methods: This retrospective study included 100 pediatric patients recently diagnosed with head and neck tumors. All patients underwent preoperative conventional magnetic resonance imaging (MRI) and DWI. Each lesion was evaluated according to signal characteristics, enhancement pattern, and diffusivity. The average apparent diffusion coefficient (ADC) obtained from each tumor was compared to the histological diagnosis of benign, locally malignant, or malignant categories. Results: Our retrospective study showed a significant negative correlation between average ADC and tumor histopathologic diagnosis (P < 0.001, r = -0.54). The mean ADC values of benign, locally malignant lesions, and malignant tumors were 1.65 ± 0.58 × 10−3, 1.43 ± 0.17 × 10−3, and 0.83 ± 0.23 × 10−3 mm2 s−1, respectively. The ADC values of benign and locally malignant lesions were overlapped. We found a cut-off value of ≥1.19 × 10–3 mm2s−1 to differentiate benign from malignant pediatric head and neck masses with a sensitivity of 97.3’, specificity of 80.0’, positive predictive value of 94.7’, and negative predictive value of 88.9’. Conclusion: Diffusion-weighted MRI study is an accurate, fast, noninvasive, and nonenhanced technique that can be used to characterize head and neck lesions. DWI helps to differentiate malignant from benign lesions based on calculated ADC values. Additionally, DWI is helpful to guide biopsy target sites and decrease the rate of unnecessary invasive procedures

Patterns of central nervous system complications of post-hematopoietic stem cell transplant in pediatric oncology patients: a single institute experience

Abstract Background Hematopoietic stem cell transplant (HSCT) has been increasingly used in the last few decades, with improved success in offering a cure. CNS complications are an important contributor to morbidity and mortality in HSCT patients. The aim of the study was to evaluate the role of imaging in the detection and assessment of CNSC (central nervous system complications) after HSCT in pediatric oncology patients. The study included consecutive pediatric patients who underwent HSCT for hematologic or solid malignancies at CCHE-57357 (Children Cancer Hospital–Egypt 57357) from January 2011 to March 2019. The age of the patients in the study ranged from 0.9 to 25 years (median age 6.5 years). CT (computed tomography) and/or MRI (magnetic resonance imaging) studies were evaluated for the detection and characterization of CNSC. Results The incidence of post-HSCT CNSC was 13% with a day 100 and 5-year cumulative incidence of 9.3 and 12.5%, respectively. The most commonly observed CNSC detected was disease recurrence, followed by PRES (Posterior reversible encephalopathy syndrome). CNS recurrence of the initial diagnosis, atrophy, and infection were more common at the > 100-day post-HSCT transplant period, while PRES was much more common at < 100-day post-HSCT. Conclusion CNS complications are an important contributor to morbidity and mortality in HSCT patients that require MRI protocols distinctively tailored for each patient, clinical suspicion, and proper imaging assessment for early detection and follow-up

Influence of Gibberellic acid and Methionine on growth, flowering quality, leaf anatomical structure and genetic diversity of Chrysanthemum morifolium Ramat plant

Ornamental plants are grown all over the world. In most countries, Chrysanthemum is considered one of the most popular cuts and potted flowers. Plants were sprayed with gibberellic acid (GA3) at concentrations (100, 200, and 300 ppm) and methionine (ME) at levels (200, 400, and 600 ppm), as bio-growth stimulants in the pre-blooming stage. The morphological and flowering parameters significantly increased by increasing the concentration of GA3. The highest values of K%, P%, total carbohydrates content, total phenols, total chlorophylls, and carotenoids in the leaf were obtained from gibberellic acid treatment at the rate of 300 ppm, while methionine at 600 ppm gave the highest value of protein in flowers. Also, various levels of gibberellic acid application significantly showed variation for days to initiation of Chrysanthemum flowers. The results of leaf anatomy showed an increase in most characteristics such as (thickness of the main vein, lamina, and spongy tissue) under study when spraying with gibberellic acid, especially at the concentration of 300 and methionine 600 ppm; respectively compared with control. Furthermore, inter-simple sequence repeat (ISSR) analysis has provided a powerful molecular marker for identifying variation with control and the best treatments. Therefore, the utilization of 300 ppm GA3 a plant growth regulator and 600 ppm ME an amino acid, these treatments are recommended to enhance Chrysanthemum parameters which lead to increasing its economic value as cut flowers and flowering potted plants as well as pharmaceuticals industries and multi-chemical uses.Keywords: Cut flowers; bio-growth stimulants; ISSR; leaf anatomy, growth regulators