Epilepsy in patients with insulin-dependent diabetes and relation to glutamic acid decarboxylase 65

Objectives:To report if the association of epilepsy in pediatric patients (below the age of 15 years) with Insulin-dependent Diabetes (IDDM) at King Fahad Medical City (KFMC) is higher than the prevalence of epilepsy in the same age group (who have no IDDM) in our community. Consequently, we would determine if there is a relationship between the presence of epilepsy in diabetic children and the presence of positive antiGAD65 antibodies.Methods:This cohort study included 305 pediatric patients below the age of 15 years with Insulin-dependent Diabetes Mellitus (IDDM). They were randomly recruited at the Pediatric Endocrinology Clinic in KFMC. The patients’ caregivers were given a questionnaire between December 2015 till March 2019 to determine the seizure disorder history. There was also a retrospective review of 214 patients’ files for anti-GAD 65 positivity.Results:Our study found a significant relation between the presence of epilepsy in children with IDDM. Therefore, we could confirm the relationship between the existence of epilepsy in children with IDDM and having positive GAD65 antibodies.Conclusion:Our study supports the presence of consistent relation between having IDDM and having epilepsy in children and between the latter and the presence of positive GAD65 antibodies.

Insulin dependent diabetes Mellitus (IDDM) is a common condition in children and adolescents worldwide and so is epilepsy.1,2 Recently, there were increasing reports suggesting a potential association between having IDDM and the occurrence of epilepsy.3 Their association might represent simply a chance to relate their underlying mechanisms. However, the cause-effect relationship is not fully well defined. Literature from other countries have shown the increased prevalence of seizure disorders in this group of patients.4,5 There are scarce studies in the literature investigating IDDM characteristics contributing to having epilepsy, including positive GAD 65 antibodies. In this study that ran in King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia (KSA) we are aiming to determine if the prevalence of epilepsy among 1DDM children under the age of 15 years (in our center) is higher than controls (same age without IDDM), and to check the positivity of anti-GAD 65 amongst those patients in order to find if there is a relationship between epilepsy in children with diabetes and the presence of positive GAD65 Antibodies.     

Ocular dysfunctions and toxicities induced by antiepileptic medications: Types,pathogenic mechanisms,and treatment strategies

Introduction: Ocular dysfunctions and toxicities induced by antiepileptic drugs (AEDs) are rarely reviewed and not frequently received attention by treating physicians compared to other adverse effects (e.g. endocrinologic, cognitive and metabolic). However, some are frequent and progressive even in therapeutic concentrations or result in permanent blindness. Although some adverse effects are non-specific, others are related to the specific pharmacodynamics of the drug.

Areas covered: This review was written after detailed search in PubMed, EMBASE, ISI web, SciELO, Scopus, and Cochrane Central Register databases (from 1970 to 2019). It summarized the reported ophthalmologic adverse effects of the currently available AEDs; their risks and possible pathogenic mechanisms. They include ocular motility dysfunctions, retinopathy, maculopathy, glaucoma, myopia, optic neuropathy, and impaired retinal vascular autoregulation. In general, ophthalmo-neuro- or retino-toxic adverse effects of AEDs are classified as type A (dose-dependent), type B (host-dependent or idiosyncratic) or type C which is due to the cumulative effect from long-term use.

Expert opinion: Ocular adverse effects of AEDs are rarely reviewed although some are frequent or may result in permanent blindness. Increasing knowledge of their incidence and improving understanding of their risks and pathogenic mechanisms are crucial for monitoring, prevention, and management of patients’ at risk.     

Age-related variations in gene expression patterns of renal cell carcinoma

Background

Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.

Impact of ceftazidime restriction on gram-negative bacterial resistance in an intensive care unit

The present study included three periods: (1) a 12-month prerestriction and control period in 2001; (2) a 12-month restriction period with reduced ceftazidime prescribing in favor of piperacillin-tazobactam (2002); (3) and a 24 month postrestriction period (2003–2004). Note that, for results, P represents the difference between 2002 and 2001; P′, the difference between 2003 and 2001; and P″, the difference between 2004 and 2001. No changes in hygiene practices were observed during these three periods. The purpose of this study was to assess the effect of reducing ceftazidime use in an intensive care unit (ICU) upon Gram-negative bacterial resistance, particularly as regards Pseudomonas aeruginosa. During the three periods of the study, patients were similar concerning age, Simplified Acute Physiology Score (SAPSII), the site of nosocomial infection, and the requirements for mechanical ventilation (75% in 2001, 76% in 2002, 74% in 2003, and 85% in 2004). The most commonly isolated pathogens were P. aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae. The use of ceftazidime decreased significantly from 12.6% in 2001 to 9% in 2002, to 3% in 2003 (P′ = 0.0009), and 2.6% in 2004 (P″ = 0.0001) in favor of piperacillin-tazobactam (0% 2001 to 3.7% in 2003; P′ = 0.002; and 5% in 2004; P″ = 0.0001). Simultaneously, we observed a significant decrease in isolates of P. aeruginosa resistant to piperacillin-tazobactam (P = 0.03; P′ = 0.004; P″ = 0.009), and those resistant to imipenem in 2003 (P′ = 0.008). We also noted a significant decrease in A. baumannii isolates resistant to ceftazidime (P′ = 0.01; P″ = 0.0004) and those resistant to imipenem in both 2002 and 2004 (P = 0.03; P″ = 0.04), and a considerable decrease in isolates of Klebsiella pneumoniae producing expanded spectrum betalactamase (ESBL) in 2003 and 2004 (P′ = 0.04; P″ = 6.10⁻⁵). In contrast, we noted an increase in penicillinase-producing isolates of K. pneumoniae, from 6% in 2001 to 16% in 2002 (p = 0.01), 20% in 2003 (P′ = 0.001), and 32% in 2004 (P″ = 10⁻⁶). We concluded that restriction of ceftazidime use was demonstrated to be efficient in reducing antimicrobial resistance, especially to K. pneumoniae ESBL.     

Impaired helix 12 dynamics due to proline 892 substitutions in the androgen receptor are associated with complete androgen insensitivity

Human Molecular Genetics (2006) 15, 921–931;     

Diabetes mellitus. II: Routine chest radiography.

Chest radiographs of 43 consecutive diabetic patients were evaluated with a view to determine their role as a routine investigation of patients with diabetes mellitus. 22 (51.2%) patients had normal chest radiographs. The remaining 21 patients had 61 abnormalities found in their chest radiographs. 26 (42.6%) of these were significant abnormalities while 35 (57.4%) were non-significant. Of the former, 42.3% were due to cardiomegaly while in the latter group, aortic unfolding was the main finding. Radiological abnormalities were more commonly observed in patients aged 40 years and over, than in those below, with a ratio of 3:1. Chest radiographs corroborated clinical diagnosis in 19 of the 21 cases in whom abnormalities were observed. This study shows that routine chest radiograph in diabetic patients is useful in those with clinical symptoms and in older diabetics above the age of 40 years.     

Enantioselective metabolism and cytotoxicity of R-ifosfamide and S-ifosfamide by tumor cell-expressed cytochromes P450.

The anticancer prodrug ifosfamide (IFA) contains a chiral phosphorous atom and is administered in the clinic as a racemic mixture of R-IFA and S-IFA. Hepatic cytochrome P450 (P450) enzymes exhibit enantioselective preferences in the metabolism of R-IFA and S-IFA; however, the impact of this selectivity on P450-dependent anticancer activity is not known. Presently, the metabolism and cytotoxicity of R-IFA and S-IFA were determined in 9L gliosarcoma and Chinese hamster ovary tumor cells expressing an IFA-activating P450 enzyme and by in vitro steady-state kinetic analysis using cDNA-expressed P450 enzymes. Tumor cells expressing P450 enzyme CYP3A4 were the most sensitive to R-IFA cytotoxicity, whereas tumor cells expressing CYP2B1 or CYP2B6 were most sensitive to cyclophosphamide (CPA), an isomer of IFA. Correspondingly, CYP3A4-expressing cells and cDNA-expressed CYP3A4 metabolized R-IFA to yield the active, 4-hydroxylated metabolite at a 2- to 3-fold higher rate than they metabolized S-IFA or CPA. CYP2B cells and cDNA-expressed CYP2B enzymes metabolized CPA almost exclusively by 4-hydroxylation, whereas R-IFA and S-IFA were substantially converted to inactive, N-dechloroethylated metabolites. Further investigation revealed that CYP3A1, a rat enzyme, exhibited superior kinetic properties compared with the human enzyme CYP3A4, with R-IFA and S-IFA both metabolized with high catalytic efficiency by 4-hydroxylation and with a K(m) value of 200 microM, approximately 5-fold lower than CYP3A4. Based on these kinetic parameters and metabolic profiles, R-IFA is expected to exert greater anticancer activity than S-IFA or CPA against tumors that express CYP3A enzymes, whereas tumors expressing CYP2B enzymes may be more sensitive to CPA treatment.     

Hibiclens keratitis

Presumed accidental corneal exposure to Hibiclens (chlorhexidine 4% and detergent) in two patients resulted in severe and permanent corneal opacification. We investigated the corneal toxicity of Hibiclens by gross, biomicroscopic, and histopathologic studies of rabbit eyes exposed to Hibiclens for varying time intervals ranging from five to 15 minutes. Severe, irreversible, and progressive corneal damage resulted in all eyes studied.