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.     

Documenting asthma severity: do we get it right?

BACKGROUND: The 1997 National Asthma Education and Prevention Program (NAEPP) recommends a severity classification scheme to optimize the use of anti-inflammatory therapy for persistent asthma. Physician documentation of asthma severity is often used as a quality assurance measure. OBJECTIVE: To test the hypothesis that physician documentation of asthma severity is associated with appropriate use of anti-inflammatory therapy. DESIGN/METHODS: Setting: inner-city academic health center. First, we reviewed a consecutive sample of charts of scheduled pediatric patients. Then, we administered a structured parent survey regarding the child's asthma symptoms and current asthma therapy. We used NAEPP guidelines to classify patients' severity of asthma. The main outcome measure was appropriate use of anti-inflammatory therapy. Appropriate therapy was defined as: (1) mild persistent asthmatics using anti-inflammatory therapy, and (2) moderate-severe persistent asthmatics using inhaled steroids. Chart classification of asthma severity was compared with the NAEPP-applied classification. RESULTS: Of 784 charts, 214 (27%) were asthmatic. Of these, 176 (82%) were surveyed. The mean age was 7.4 years; 61% were males. Severity classification was documented in 77% of charts. Chart documentation differed significantly from survey classification for the same patients: (mild intermittent 54% vs. 40%, mild persistent 21% vs. 14%, moderate persistent 24% vs. 36%, severe persistent 1% vs. 10%; all p < .001). Correctly classified patients were more likely to be on appropriate therapy. CONCLUSIONS: Physicians underestimated the severity classification of asthmatic patients. Incorrect classification was associated with inappropriate asthma therapy. These findings have implications for the institution of asthma quality improvement programs.     

Does off-pump coronary artery bypass reduce the incidence of post-operative atrial fibrillation? A question revisited.

Atrial fibrillation (AF) is the most common post-operative complication in patients undergoing coronary artery bypass grafting, with an increased incidence associated with advancing age. This study aims to determine whether off-pump coronary artery bypass (OPCAB) reduces the incidence of AF in a generalized population (mean age <70 years). A meta-analysis was performed including all randomised and propensity score matched non-randomised studies published between 2001 and 2003 reporting a comparison between the two techniques in a generalised patient group (average age <70 years). The primary outcome of interest was post-operative AF. Sensitivity analysis was performed to evaluate consistency of the calculated treatment effect. Fourteen studies fulfilled our inclusion criteria, including a total of 16,505 subjects. The incidence of AF was 19% (1612/8265) in the off-pump group versus 24% (1976/8240) in the on-pump group. When considering only the 11 randomised studies (2207 subjects), we found a significant reduction in the incidence of post-operative AF in the off-pump group using a random-effect model (odds ratio (OR)=0.60, 95% confidence interval (CI)=0.45-0.82, and chi-square of heterogeneity=18.02, P=0.05). Sensitivity analysis highlighted one randomised study causing funnel plot asymmetry, exclusion of which resulted in a significant reduction in the incidence of post-operative AF in the off-pump group (OR=0.71, 95% CI=0.57-0.90), with a non-significant heterogeneity of 3.91 (P=0.92). When only studies of high quality were considered (898 patients), no significant difference was seen between on and off-pump groups (OR=0.78, 95% CI=0.57-1.07, and heterogeneity=0.53, P=0.91). This may be due to small number of patients in this group. Our results suggest that although OPCAB surgery may reduce the incidence of post-operative AF in a generalised population (age <70 years) this finding is not clearly supported by high quality randomised trials. Although previous evidence suggests that the incidence of post-operative AF is reduced in an elderly population (>70 years) with off-pump surgery, our results show that the evidence is less clear in a younger population group. The question of whether off-pump surgery in this patient group results in a lower rate of post-operative AF remains to be answered by further high quality randomised research.     

Dobutamine improves thoracic aortic blood flow during off-pump coronary artery bypass surgery: results of a prospective randomised controlled trial.

OBJECTIVE: Dobutamine is commonly used to improve ventricular performance in cardiac surgery. The aim of this prospective randomised controlled study was to assess the effectiveness of using low doses of dobutamine during off-pump coronary artery bypass (OPCAB) surgery in order to reduce haemodynamic compromise due to heart displacement. METHODS: Thirty-two patients undergoing elective coronary artery bypass grafting (CABG) surgery using OPCAB technique for more than two vessels were approached and recruited. We analysed the changes in the thoracic aortic blood flow (TABF) during OPCAB using transoesophageal Doppler and by other conventional monitoring methods as cardiac output, invasive pulmonary and radial pressures and mixed venous oxygen saturation. RESULTS: The two groups were similar in preoperative characteristics. No postoperative complications were observed in the study patients. The heart rate, right atrial pressure, cardiac output measured by thermodilution and TABF changed significantly during the procedure. Also significant changes in descending thoracic aortic diameter were observed. The postoperative creatinine was significantly lower in the dobutamine group (P=0.04). Dobutamine was found responsible for the improvement in the descending TABF (P=0.006). CONCLUSIONS: This study showed that intra-operative intravenous infusion of dobutamine at 5 microg/kg per min in routine OPCAB patients safely increased cardiac output even without such changes been detected by conventional monitoring methods.     

Glucose-deprivation-induced [3H]D-aspartate release from isolated bovine and human retinae.

The glucose deprivation-induced release of [3H]D-aspartate was studied in bovine and human retinas in a superfusion apparatus. [3H]D-aspartate release was significantly increased upon omitting glucose in the superfusion buffer. This effect was dependent on external Ca2+ because L- and N-type Ca2+-channel blockers, such as diltiazem (1 microM), nitrendipine (1 microM), and omega-conotoxin (100 nM), significantly reduced the effect of glucose-deprivation induced release of [3H]D-aspartate. Furthermore, while glutamate receptor agonists (L-glutamate, N-methyl-D-aspartate, but not kainate) potentiated the effects of glucose deprivation, antagonists (MK-801, MCPG, ifenprodil, and L-AP3) at these receptors blocked the glucose deprivation-induced release process. Taken together, these studies have demonstrated that under conditions of glucose deprivation, as may happen during ischemic events in vivo, the retinal glutamatergic nerve endings and/or glial cells promote the efflux of [3H]D-aspartate into the extracellular environment. This process appears to be receptor-mediated and dependent on extracellular Ca2+ and is similar to previous reports pertaining to brain tissues.     

Term delivery in a woman with severe congenital neutropenia, treated with growth colony stimulating factor

The patient was diagnosed in childhood as having severe congenital neutropenia and had recurrent admissions with severe infections. In 1987, prior to getting married, she was sterilized. She continued to require i.v. antibiotics when she contracted a severe infection. On one occasion, she was treated with growth colony stimulating factor (G- CSF). Her increased neutrophil count was sustained following this treatment. In June 1993, she wished to start a family and underwent in- vitro fertilization (IVF) treatment. G-CSF was given prior to oocyte retrieval. She conceived on her first cycle and an ultrasound scan revealed a singleton pregnancy. Throughout the course of the pregnancy, her white cell count was monitored closely and remained at <1.0x10(9)/l. The pregnancy progressed uneventfully and at 37 weeks gestation she was admitted for G-CSF injections. At 38 weeks she was delivered of a boy weighing 3350 g, by elective Caesarean section. His white cell count was normal. This is the first case of G-CSF being used before conception and during pregnancy in a patient with congenital neutropenia. It shows that advances in cytokine therapy and close interdisciplinary liaison can lead to a successful outcome and help patients, who would otherwise remain childless, to achieve a family.      

Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy

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Concentrations of domestic mite and pet allergens and endotoxin in Palestine

BACKGROUND: A few studies have compared indoor allergens and endotoxin levels between urban and rural settings as important determinants for asthma and atopy in children. However, no study was done in the Middle East or investigated refugee camps. METHODS: As part of a nested case-control study in Ramallah in 2001, we measured house dust mite and pet allergens, as well as endotoxin in dust collected from 110 children's mattresses and living room floors. RESULTS: Geometric mean (GM) concentrations of Dermatophagoides pteronyssinus (Der p1) antigen were 4.48 microg/g in mattress dust and 1.23 microg/g floor dust. The highest Der p1 levels were seen in refugee camps. Concentrations of Dermatophagoides farinae antigen (Der f1) were much lower (<0.08 microg/g dust). Concentrations of cat allergen (Fel d1) were highest in villages, and those of dog allergen (Can f1) were highest in mattresses from cities and in floor dust from refugee camps. GM of endotoxin levels were 25.7 EU/mg in mattress dust and 49 EU/mg dust in floor dust. CONCLUSIONS: Concentrations of Der p1 were high compared to Western European countries, but were lower compared to UK and Australia. Levels of pet allergens were lower than in Western Europe. Endotoxin levels were higher compared to developed countries. Indoor environmental factors such as dampness seemed to be important determinants for allergen and endotoxin, but living habits such as lack of mattress cover appeared unimportant.     

Molecular anatomy of the β' subunit of the E. coli RNA polymerase: identification of regions involved in polymerase assembly

Background : The E. coli RNA polymerase is a multisubunit enzyme, which is present in two different forms: the catalytic competent core enzyme (α₂ββ ') and the promoter selective holoenzyme (α₂ββ 'σ). Correct assembly of individual subunits into core or holoenzyme is essential for the function of this enzyme.
Results : Mutant β ' proteins truncated near the centre or at the C-terminus were able to form stable core enzyme-like complexes under reconstitution conditions. Mutant β ' proteins lacking the region between amino acids 201–477 failed to form holoenzyme complexes while retaining the ability to form core enzyme complexes. Furthermore, free β ' subunit interacted with free σ subunit to form a stable β 'σ subassembly. Removal of amino acids 201–477 from the β ' subunit strongly interfered with this interaction.
Conclusion : Our results suggest that the N-terminal region of the β ' subunit is involved in the assembly of core enzyme. The region between amino acids 201 and 477 on β ' may be directly or indirectly involved in the interaction between the β ' subunit and the σ subunit.