The association of TMPRSS6 gene polymorphism with iron status in Egyptian children (a pilot study).

Several studies have shown association of single nucleotide polymorphisms (SNPs) of hepcidin regulatory pathways genes with impaired iron status. The most common is in the TMPRSS6 gene. In Africa, very few studies have been reported. We aimed to investigate the correlation between the common SNPs in the transmembrane protease, serine 6 (TMPRSS6) gene and iron indicators in a sample of Egyptian children for identifying the suitable candidate for iron supplementation.Patients and methods One hundred and sixty children aged 5-13 years were included & classified into iron deficient, iron deficient anemia and normal healthy controls. All were subjected to assessment of serum iron, serum ferritin, total iron binding capacity, complete blood count, reticulocyte count, serum soluble transferrin receptor and serum hepcidin. Molecular study of TMPRSS6 genotyping polymorphisms (rs4820268, rs855791 and rs11704654) were also evaluated.Results There was an association of iron deficiency with AG of rs855791 SNP, (P = 0.01). The minor allele frequency for included children were 0.43, 0.45 & 0.17 for rs4820268, rs855791 & rs11704654 respectively. Genotype GG of rs4820268 expressed the highest hepcidin gene expression fold, the lowest serum ferroportin & iron store compared to AA and AG genotypes (p = 0.05, p = 0.05, p = 0.03 respectively). GG of rs855791 had lower serum ferritin than AA (p = 0.04), lowest iron store & highest serum hepcidin compared to AA and AG genotypes (p = 0.04, p = 0.01 respectively). Children having CC of rs11704654 had lower level of hemoglobin, serum ferritin and serum hepcidin compared with CT genotype (p = 0.01, p = 0.01, p = 0.02) respectively.Conclusion Possible contribution of SNPs (rs855791, rs4820268 and rs11704654) to low iron status.

Low Dose Iron Therapy in Children with Iron Deficiency: DNA Damage and Oxidant Stress Markers.

Conflicting data are available regarding oral iron therapy in iron deficiency (ID), iron deficiency anemia (IDA) and its relation to DNA damage, oxidative stress and antioxidant markers. Our aim was assessment of DNA damage, oxidative stress and anti-oxidant markers in children with ID and IDA before and after low dose iron therapy. The study was conducted in two stages, first stage was assessment of DNA damage using comet assay, malondialdehyde (MDA) and anti-oxidant enzymes levels (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) & total antioxidant capacity (TAC) in thirty-nine children with IDA, forty-five children with ID without anemia and sixty healthy controls. Second stage was assessment of previous markers together with hematological response following oral therapy with 10 mg/day ferric ammonium citrate for 8 weeks. Before treatment, there was no significant difference between the three groups regarding MDA, GPx, SOD, CAT and TAC. A significant increase was detected in the DNA damage in the 2 groups compared to control (p < 0.005). Following iron therapy, hematological parameters was improved together with a significant increase in GPx (P = 0.04), SOD (p = 0.002), TAC (P = 0.001) and non-significant reduction in DNA damage in IDA group. There was a significant increase in SOD (p = 0.001) & TAC (p = 0.001) and significant decrease in DNA damage (p = 0.001) in ID group. Low dose iron therapy could be sufficient to improve antioxidant status and DNA damage together with correction of hematologic indices.

Hypervirulent Klebsiella pneumoniae as a hospital-acquired pathogen in the intensive care unit in Mansoura, Egypt.

INTRODUCTION: Hypervirulent Klebsiella pneumoniae (hvKP) are variants of K. pneumoniae that come up worldwide. hvKP is known in community-acquired infections but little is known about its role in hospital-acquired (HA) infections. The aim of this study was to evaluate the frequency of hvKP among HA K. pneumoniae infections in the intensive care unit (ICU) and to compare virulence and antibiotic susceptibility between hvKP and classical K. pneumoniae (cKP). METHODS: String test, biofilm formation, serum bactericidal assay, capsular polysaccharide genes (K1, K2, K5, K20, K54, K57), virulence genes: rmpA, rmpA2, iucA, iroB and antimicrobial susceptibility were assessed in HA K. pneumoniae strains isolated from the ICU in Mansoura, Egypt. RESULTS: Probable hvKP represented 4 out of 65 (6.2%) K. pneumoniae. K1 and K2 genes were present in 2 and 1 isolate respectively in probable hvKP. rmpA genes were significantly associated with hvKP; at the same time biofilm production and serum resistance were not significantly associated with the hypervirulent group. There was no significant difference between hvKP and cKP strains in terms of resistance pattern. CONCLUSION: hvKP in critically ill patients from the ICU may form a new threat especially in the presence of antibiotic resistance. Although the validity of the string test in detecting metastatic Klebsiella is questionable, it is a simple and easy test that can be done in any laboratory indicating the presence of this organism. Serotypes and genomic background may provide helpful and confirmatory tools to diagnose hvKP.

Adipokines Vaspin and Visfatin in Obese Children.

BACKGROUND: Adipokines provides new insights about the physiology, pathology and treatment of obesity. AIM: We investigated the association between serum vaspin and serum visfatin concentrations with obesity in Egyptian children. MATERIAL AND METHODS: Twenty two obese children with body mass index (BMI) above 95th percentile; 11 males and 11 females were included in this study. Their mean age was 9.18 ± 2.8 years. After general clinical examination, fasting blood glucose, triglycerides, total cholesterol and high density lipoprotein cholesterol were measured in cases and controls (n=11). Fasting insulin, vaspin and visfatin were detected using ELIZA. Insulin resistance was estimated by Homeostasis model assessment method (HOMA-IR). RESULTS: Blood pressure, in both systolic and diastolic measurements was elevated significantly in obese children. Significant elevation of serum insulin and insulin resistance (HOMA/IR) were observed in obese children too. Vaspin and visfatin showed significant elevation in obese children than controls. Significant positive correlations were detected between visfatin and BMI, waist circumference, hip circumference and HOMA/IR. We found that Vaspin and visfatin are higher in obese children. CONCLUSION: Visfatin but not vaspin correlates positively with waist circumference and HOMA/IR in obese children.

Risk Association between TNF-α-308 G>A and IL-6-174 G/C Polymorphisms and Recurrent Transient Ischemic Attacks.

Transient ischemic attack (TIA) is a brief cerebral ischemic incident. This study assesses the role of TNF-α and IL-6 single nucleotide polymorphisms (SNPs) as predictors of recurrent TIAs that have high risk of developing stroke. The current study enrolled 54 high risk (according to frequency of TIA) TIA (group1), 52 low risk TIA patients (group2) and 34 controls (group3). Polymerase chain reaction (PCR) for DNA amplification was done followed by restriction endonuclease analysis to detect SNPs of TNF-α-308 G > A and IL-6-174 G/C. TNF-α serum level was analysed by ELISA. Significant increase of TNF-α-308 G > A allele (group1 compared to group2 and control P=0.0001) and genotype TNF-α-308 AA (P≤0.05) were detected. IL6 allele polymorphism revealed insignificant SNPs. The serum TNF-α was higher in group1 compared to control and group2 and as well in TNF-α-308 AA variant in high risk group (P≤0.05). It is concluded that TNF-α-308 G > A SNP might have a role in predicting recurrent TIA with impact on preventive measures of stroke development.

Thyroid volumes and iodine status in Egyptian South Sinai schoolchildren.

INTRODUCTION: The determination of goitre prevalence in children by ultrasonography is an important tool for considering iodine deficiency disorders. Our objective was to describe measurements of thyroid volumes by ultrasonography in Egyptian South Sinai schoolchildren and compare these with the WHO/International Council for the Control of Iodine Deficiency Disorders normative thyroid volume criteria (WHO/ICCIDD). MATERIAL AND METHODS: Cross-sectional thyroid ultrasonographic data of 719 schoolchildren (339 boys and 380 girls), aged 6-12 years from five cities in South Sinai (El Tur (T), Abu Redis (R), Ras Sudr (S), Saint Katherine (SK), and Nwebaa (N)). Age/sex and body surface area/sex specific upper limits (97(th) percentile) of normal thyroid volume were derived and urinary iodine (UI) was measured. RESULTS: The median value of urinary iodine was 150 µg/l. Comparing WHO/ICCIDD thyroid volume references to Egyptian South Sinai schoolchildren resulted in goitre prevalence of 10.6% using age/sex specific and 13.48% using body surface area/sex specific cut-off values. The prevalence of goitre was 20.0% in S, 16.3% in R, 10.8% in N, 9.9% in T, and 10.5% in SC. Upper limits of normal (97(th) percentile) thyroid volume from South Sinai schoolchildren calculated using BSA, sex, and age were higher than the corresponding WHO/ICCIDD. CONCLUSIONS: Prevalence of goitre is high in South Sinai schoolchildren. The body surface area reference should be preferred to the reference based on age. South Sinai schoolchildren had larger thyroids than WHO/ICCIDD thyroid volumes, perhaps due to hard polluted water with a high fluorine level.

Schistosomal myeloradiculopathy due to Schistosoma mansoni: Report on 17 cases from an endemic area.

BACKGROUND: After malaria, schistosomiasis is the second most prevalent tropical disease. The prevalence of oviposition in CNS of infected persons varies from 0.3 to 30%. The conus medullaris is a primary site of schistosomiasis, either granulomatous or acute necrotizing myelitis. OBJECTIVE: To report the clinical, radiological, and laboratory results of spinal cord schistosomiasis (SCS) and to design proper therapeutic regimens. MATERIALS AND METHODS: Seventeen patients (13 males and four females) with SCS were enrolled between 1994 and 2009 at Mansoura University Hospitals. Their median age at diagnosis was 19 years (13-30 years). Independent neurological, radiological, and laboratory assessments were performed for both groups, excluding pathological confirmation that was done earlier in eight patients (Group 1). In the group 2 (nine patients), indirect hemagglutination (IHA) test for bilharziasis in blood and cerebrospinal fluid (CSF) was performed. Higher positive titer in CSF than serum indicated SCS plus induction of antibilharzial and corticosteroid protocols for 12 months with a three-year follow-up. RESULTS: Rate of neurological symptoms of granulomatous intramedullary cord lesion was assessed independently in 16 cases and acute paraparesis in one case. All patients in group 2 had positive IHA against Schistosoma mansoni with median CSF and serum ranges 1/640 and 1/320, respectively. Seven patients (41.18%) had complete recovery, eight patients (47.06%) showed partial recovery, and no response was reported in two patients (11.76%) (P = 0.005). There was no recorded mortality in the current registry. CONCLUSIONS: Rapid diagnosis of SCS with early medical therapies for 12 months is a crucial tool to complete recovery.

Bone density, body composition, and markers of bone remodeling in type 1 diabetic patients.

OBJECTIVE: To assess bone mineral density (BMD), body composition by dual X-ray absorptiometry (DXA), and various biochemical markers of bone growth and resorption in a group of children with type 1 diabetes mellitus (T1DM). PATIENTS AND METHODS: The study included 47 patients with T1DM and 30 age- and sex-matched controls. Anthropometric measurements, biochemical markers for bone formation, bone resorption and DXA were done for all patients and controls. RESULTS: Of our diabetes patients, seven (16.7 %), three (7.3 %), and 17 (41.5%) met diagnostic criteria for osteopenia at the right femur, lumbar spine and total body, respectively. On the other hand, osteoporosis as defined by the WHO criteria was diagnosed in 21 patients (51.2%) at the total body by DXA. Lean body mass and lean fat ratio were lower, while, total fat mass, abdominal fat%, soft tissue fat mass%, and fat/lean ratio were higher in diabetics compared to controls. Also, our patients showed lower serum osteocalcin, osteoprotegerin, procollagen type 1, and higher urinary deoxypyridinoline. Pubertal (diabetics and controls) have higher BMD and BMC than prepubertal. CONCLUSION: Diabetic patients had a low BMD after adjustment (Z score), low bone formation and high bone resorption markers. Diabetes control and increase in BMI leads to a decrease in the incidence of low bone mineral density. Diabetes causes an increase in body fat especially abdominal fat which leads to an increase in insulin resistance and decrease in lean mass.

Bone mineral density, bone turnover markers, lean mass, and fat mass in Egyptian children with congenital adrenal hyperplasia.

INTRODUCTION: Aim of this paper is to assess bone mineral density (BMD) and body composition, by dual energy X-ray absorptiometry (DXA), and various markers of bone growth, in a group of children with congenital adrenal hyperplasia (CAH) on long-term glucocorticoid therapy. MATERIAL AND METHODS: A case-control study included thirty patients with CAH with different states of metabolic control. Their mean age was 7.5 ±4.2 years. All patients are subjected to BMD using DXA at the neck of the femur and lumbar spine. A blood sample was taken for assessment of osteocalcin, osteoprotegerin, and procollagen type 1, as markers of bone formation, as well as RANKL and urinary deoxypyridinoline (DPD), as markers of bone resorption. RESULTS: We found no difference in BMD in patients and control subjects; however, patients showed significantly lower serum osteocalcin (p = 0.008) and osteoprotegerin (p = 0.0001) and significantly higher serum RANKL levels (p = 0.0001). Our results show that patients had significantly lower lean body mass (p = 0.005) and fat/lean ratio (p = 0.008) compared to matched controls. The duration of treatment showed a significant negative correlation with procollagen type 1 (r = -0.49, p = 0.02) and lean mass % (r = -0.43, p = 0.04); however, it showed a significant positive correlation with total fat mass % (r = 0.6, p = 0.0006), and fat/lean ratio (r = 0.43, p = 0.04). Dose of steroid had a significant positive correlation with BMI SDS (r = 0.4, p = 0.02). CONCLUSIONS: Bone mineral density is normal but bone turnover is low in patients with CAH. There is an increase in fat/lean mass in patients with CAH.

The effects of L-thyroxin replacement therapy on bone minerals and body composition in hypothyroid children.

INTRODUCTION: Prolonged treatment with levothyroxine 4 (L-T4) is a well known risk factor for osteoporosis. Patients on L-T4 replacement occasionally have a subnormal TSH, which carries a risk of development of bone loss. Thyroid hormones directly affect bone cells, stimulating osteoclastic and osteoblastic activity with a predominance of bone resorption and decrease of bone mineral density (BMD). MATERIAL AND METHODS: The study included 35 hypothyroid patients with mean age 11.57 ±5.06, while 26 age- and sex-matched children served as controls. Dual energy X-ray absorptiometry (DXA) was done to detect the bone mineral density (BMD), bone mineral content (BMC) and Z score in lumbar and femur neck regions. Body composition was also studied by DXA. Calcium, phosphorus, osteocalcin as a bone formation marker, osteoprotegerin as an indicator of osteoclast activity and urinary deoxypyridinoline as a bone collagen breakdown marker were assessed. RESULTS: No significant differences were detected in lumbar Z score (-0.12 ±0.66) and femur Z score (-0.17 ±0.58) compared to controls (-0.33 ±0.74 and -0.21 ±0.53 respectively). Bone mineral density and BMC were not significantly different from controls. No significant difference was detected between cases and controls in body composition. A positive correlation was detected between BMD and age (r=0.857, p<0.01), and with the period of treatment (r=0.766, p<0.01). A positive correlation was found between BMD and total body fat (r=0.693, p<0.01), and with abdominal fat (r=0.667, p<0.01). CONCLUSIONS: Levothyroxine 4 treatment in hypothyroid children does not alter bone metabolism and body composition.

Outcome of medical and surgical management in intractable idiopathic trigeminal neuralgia.

BACKGROUND: The neurovascular conflict in trigeminal neuralgia is an intractable condition; medical treatment is usually of long duration and can be annoying for both patients and clinicians. AIM: This prospective study was designed to assess the outcome of microvascular decompression (MVD) in patients with more than 3 years' history of intractable idiopathic trigeminal neuralgia (TN) and poor response to drugs. MATERIALS AND METHODS: Twenty-one patients (8 females and 13 males) with intractable idiopathic TN (group 1) underwent MVD and were followed up for 2 years. Group 2 (n = 15), which included 6 females and 9 males, received pharmacotherapy. The outcome responses of pain relief were evaluated using a 10-cm visual analog scale (VAS) and the Barrow Neurological Institute (BNI) scoring system. The patients' morbidity was recorded as well. RESULTS: All patients fulfilling the inclusion criteria were offered MVD surgery. Freedom from pain was achieved immediately after surgery in 95.2% (n = 20) of patients in group 1, and 90.5% (n = 19) had sustained relief over the follow-up period. There were no statistical significance recurrences or surgical complications in group 1 (P>0.5), while 53.3% (n = 8) of the subjects in group 2 showed poor response with pharmacotherapy over the same period of time and many patients experienced drug intolerance that had statistical significance (P<0.01). CONCLUSION: Early MVD in TN can help patients avoid the side effects of drugs and the adverse psychological effects of long-term pharmacotherapy and prolonged morbidity.

Blocking effects of serum reactive antibodies induced by glatiramer acetate treatment in multiple sclerosis.

Glatiramer acetate (GA) is a treatment option for multiple sclerosis. Although its mechanism of action remains unclear, evidence has emerged supporting the role of GA as an immunomodulatory drug that regulates T-cell function. It has been demonstrated that long-term GA treatment induces a serum antibody response; however, the functional properties of these 'reactive antibodies' are unknown. It has been speculated that GA-induced antibodies may have a blocking effect that can inhibit the immunologic activity of GA. This study was conducted to determine whether serum antibodies induced by GA treatment can block the in vitro immunoregulatory effects of GA on T-cell proliferation and cytokine production. Forty-two patients with relapsing-remitting multiple sclerosis who were treated with GA for 1-5 years were examined for GA antibody titres using enzyme-linked immunoabsorbent assay (ELISA). Thirty-three percent of patients developed high antibody titres [antibody binding index (ABI) = 16-64] and 14% had low antibody titres (ABI = 4) after 1 year on treatment. Results showed that purified GA antibodies blocked the stimulatory effects of GA on GA-specific T-cell lines of Th0 cytokine profile. The increase in interleukin-10 (IL-10) and IL-4 levels and the decrease in IL-12 and tumour necrosis factor-alpha levels, normally seen with GA stimulation, were reversed in the presence of GA antibodies. The study has important implications in our understanding of the potential role of high-titre GA antibodies in the treatment of multiple sclerosis.

Effects of combination therapy of beta-interferon 1a and prednisone on serum immunologic markers in patients with multiple sclerosis.

Beta-interferon (beta-IFN) has a proven treatment effect on relapsing-remitting multiple sclerosis (MS), presumably through its regulatory properties on T-cell activation and cytokine production. This paper examines whether combination therapy of beta-IFN with prednisone would enhance immunoregulatory effects of beta-IFN by measuring serum levels of selected proinflammatory cytokines and soluble T-cell activation markers associated with MS. The selected markers were analyzed in MS patients treated with beta-IFN alone (n = 22) and beta-IFN combined with a low daily dose of prednisone (n = 33), as compared with those in 27 healthy controls at baseline and at a three-month interval for one year. The study confirmed that beta-IFN treatment inhibited serum levels of tumor necrosis factor-alpha (TNFalpha) and intracellular adhesion molecule-1 (ICAM-1) in patients with MS. However, combination therapy did not significantly enhance the inhibitory effect of beta-IFN treatment on the production of TNFalpha, interleukin (IL)-12, IL-2R, and ICAM-1, while the addition of prednisone antagonized the effect of beta-IFN on up-regulation of IL-10 and soluble CD95. No difference in the occurrence of binding antibodies to beta-IFN was found between the two treatment groups. The findings are important for the understanding of the role of combination therapy in the treatment of MS.