Management of rare side effects of peginterferon and ribavirin therapy during hepatitis C treatment: a case report

Cardiac arrhythmias and syncope are rare consequence of therapy with pegylated interferon. We report a 55-year-old Egyptian woman who developed palpitation and syncopal attacks twice within 3 months after starting therapy with pegylated interferon α2b and ribavirin for the treatment of chronic hepatitis C virus. Hepatitis C virus-RNA was undetectable after 12 week. The electrocardiogram holter revealed ventricular extra-systoles on top of sinus tachycardia. pegylated interferon α2b therapy was continued but with a reduced dose. Close follow up revealed neither palpitation nor syncope and hepatitis C virus-RNA was undetectable at 24 and 48 weeks of treatment. In conclusion, our study suggests readjustment of the dose of pegylated interferon α2b therapy to avoid these serious side effects

Polyploidy in chronic lymphocytic leukemia with p53 deletion detected by fish: a case report

We report a case of chronic lymphocytic leukemia with a characteristic cytogenetics finding detected by fluorescent in situ hybridization. This case has deletion in p53 gene in 50% of interphase nuclei studied in the peripheral blood and polyploidy in 30% of cells. To our knowledge polyploidy is not commonly reported with chronic lymphocytic leukemia patients

Immunological Evaluation in Patients with Familial Mediterranean fever

OBJECTIVE: This study aimed to investigate T & B lymphocyte subsets and Natural Killer (NK) cells patterns in children with FMF versus normal control subjects, to estimate the immunoglobulins IgG, IgM, and IgA levels, and to scrutinize the possible use of Neutrophil / Lymphocyte ratio (NLR) as a marker for subclinical inflammation in FMF patients.PATIENTS AND METHODS: A group of 42 patients with FMF attending the Genetics Clinic at National Research Centre were included in this study. They were 13 males and 19 females; their age ranged from 2 to 17 years old. Normal healthy subjects within the same age and sex range were included as a control group. Complete blood picture was done for all cases, and neutrophil/ lymphocyte ratio was calculated. Flow cytometer analysis was done for CD3, CD4, CD8, CD19 and CD16 using monoclonal antibodies. Immunoglobulins IgG, IgA and IgM were estimated in serum using nephelometry.RESULTS: Positive consanguinity was present in 20 patients (47.6%). Abdominal pain was the most common manifestation followed by fever, arthritis, and red rash. CD3, CD4 and CD8 were statistically increased in patients group as compared to normal control group, while CD16 was statistically decreased.CONCLUSION: The study suggests that quantitative measurement of CD expressions of CD3, CD4 and CD8 as well as NLR might be used as valuable markers for subclinical inflammation in FMF

Serum soluble receptor of advanced glycation end products and risk of metabolic syndrome in Egyptian obese women

Obesity is one of the diagnostic criteria of metabolic syndrome (MS). It is correlated with insulin resistance (IR) and high vascular risk as well. Advanced glycation end products (AGEs) and their receptor (RAGE) play an important role in abnormal metabolic components in obese women. This study aimed to explore the serum levels of sRAGE in Egyptian obese women and compare with healthy non-obese controls and investigate the relationship between serum sRAGE, metabolic parameters, and obesity complications. The soluble form of receptor for advanced glycation end products (sRAGE), anthropometry, metabolic and biochemical biomarkers were measured in 100 obese women and 100 age-matched healthy control non-obese women. The homeostasis model assessment estimate of insulin resistance (HOMA-IR) has been determined from serum insulin and glucose values. Serum sRAGE levels were significantly lower in obese cases than controls and inversely correlated with obesity and metabolic parameters. Results of univariate and multivariate analyses for determinants of serum sRAGE levels in obese cases showed that parameters statistically and significantly related were body mass index (BMI), waist circumference (WC), LDL-C, TG, BP, HOMA-IR, ALT and AST. sRAGE is a novel biomarker for metabolic dysfunction in Egyptian obese women and might predict the future cardio-metabolic events

Association of the Pro12Ala Polymorphism with the Metabolic Parameters in Women with Polycystic Ovary Syndrome

AIM: To investigate the association of peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala polymorphism with polycystic ovary syndrome (PCOS) and its effect on the metabolic parameters in PCOS women.METHODS: The study used PCR to identify the presence of the PPARG Pro12Ala polymorphism in 100 PCOS women and 120 age-matched healthy women. All participants were subjected to anthropometry, biochemical and metabolic evaluation.RESULTS: Significant difference in the genotypes distributions of PPARG Pro12Ala polymorphism was observed among PCOS women and controls (p = 0.03). The frequency of the polymorphic allele Ala was significantly higher in PCOS cases than that in the controls (OR = 2.01, p = 0.01). The carries of the variant allele Ala in PCOS women showed significant higher values in body mass index (BMI), systolic and diastolic blood pressure, waist circumference, waist to hip ratio, sum of skin folds, fasting blood glucose, fasting blood insulin, HOMA-IR, fasting triglycerides, total cholesterol and low-density lipoprotein than non-carriers.CONCLUSION: The PPARG Pro12Ala polymorphism might contribute to the risk of PCOS and abnormal metabolic parameters and could be considered as a biomarker for early diagnosis and clinic prediction of metabolic complications

Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants.

Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1-/- mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy

Sexual dysfunction in males with hepatitis C virus: Relevance to histopathologic changes and peginterferon treatment

Background/Aim: The frequency of sexual dysfunction (SD) is not well known in patients with chronic hepatitis C virus (HCV). In spite of the fact that histological benefits of peginterferon (Peg-IFN)/ribavirin therapy are well established, the effects on sexual health are less certain. To assess the prevalence of the SD and explore its relevance to histopathologic changes and Peg-IFN treatment. Materials and Methods: The study included 100 HCV males; all the patients completed questionnaires to assess their sexual function before and during the treatment. Results: Before treatment, SD was reported only by 12 (19.4%) and 10 (29.4%) patients of early and advanced liver fibrosis, respectively. SD during HCV treatment (with Peg-IFN and ribavirin) for liver fibrosis was significant, as 24 (70.6%) out of 34 (100%) of HCV patients had advanced fibrosis but only 20 (32.3%) out of 62 (100%) patients had early fibrosis and were sexually affected (P = 0.01). SD before treatment was found in 22 (22%) patients; 16 (16%) were >40 years old and 6 (6%) patients were ≤40 years old. SD showed highly significant (P = 0.001) difference prior to and during treatment. Pre treatment, 78 (78%) patients denied any SD and only 22 (22%) were sexually affected, while during treatment, the number of patients who were sexually affected rose to 44 (44%). The rest of the group [56 (56%)] did not report any sexual impairment. Conclusion: SD was noticed during Peg-IFN and ribavirin treatment in patients with advanced liver fibrosis. Age and advanced liver fibrosis were important factors in inducing SD. This is of key importance for clinical practice as it modifies the management of HCV patients

Evaluation of DNA damage profile in obese women and its association to risk of metabolic syndrome, polycystic ovary syndrome and recurrent preeclampsia

Metabolic syndrome (MS) is a cluster of metabolic abnormalities. Obesity and MS are always accompanied by elevated oxidative stress which might affect cellular bio-molecules such as DNA. The aim of the present study is to investigate DNA damage profile in obese premenopausal women and its relation to the risk of MS, polycystic ovary syndrome (PCOS) and history of recurrent pre-eclampsia. The study included 90 obese women included cases with MS (n = 30), PCOS (n = 30) and previous history of recurrent preeclampsia (n = 30) and, age-matched healthy non-obese control women (n = 50). The assessment of leukocyte DNA damage was done by comet assay for all cases and controls. Anthropometry and biochemical parameters have been measured. Results showed that mean percent of DNA damage was significantly higher in MS, PCOS as well as in women with the recurrent preeclampsia as compared to healthy controls. The high level of mean DNA damage frequency in obese women was significantly associated with the increased number of metabolic syndrome components. Cases with 2, 3 and 3–5 components showed significantly higher levels of DNA damage than controls. Moreover, cases with 3–5 MS components showed significant higher DNA compared to those with the two components. Regarding PCOS, significant positive association between the mean frequency of DNA damage and waist circumference was observed. The study suggests that metabolic abnormalities, PCOS and recurrent pre-eclampsia might be contributed in development of DNA damage in obese women. DNA damage can serve as an early marker for obesity complications in premenopausal women. Keywords: DNA damage, Metabolic components, Obesity, PCOS, Recurrent preeclampsi

Genetic and Epigenetic Regulation of MEFV Gene and Their Impact on Clinical Outcome in Auto-Inflammatory Familial Mediterranean Fever Patients

Epigenetic modifications play a pivotal role in autoimmune/inflammatory disorders and could establish a bridge between personalized medicine and disease epidemiological contexts. We sought to investigate the role of epigenetic modifications beside genetic alterations in the MEFV gene in familial Mediterranean fever (FMF). The study comprised 63 FMF patients diagnosed according to the Tel Hashomer criteria: 37 (58.7%) colchicine-responders, 26 (41.3%) non-responders, and 19 matched healthy controls. MEFV mutations were detected using a CE/IVD-labeled 4-230 FMF strip assay. DNA methylation of MEFV gene exon 2 was measured using bisulfite modification and related to pyrin level, phenotypic picture, MEFV mutations, disease severity, serum amyloid A (SAA), CRP, ESR, disease severity, and colchicine response. Our results showed that FMF patients exhibited significantly higher methylation percentage (p p p < 0.004). High methylation percentage of the MEFV exon 2 and low pyrin concentration were correlated with disease severity, high SAA, ESR levels, H-pylori, and renal calculi. In conclusion, this study highlights the relation between high methylation percentage, reduced pyrin level, and different biomarkers in FMF, which underscores their role in the pathogenesis of FMF and could be considered as potential therapeutic targets