Risk genes and autoantibodies in Egyptian children with type 1 diabetes - low frequency of autoantibodies in carriers of the HLA-DRB1*04:05-DQA1*03-DQB1*02 risk haplotype.

BACKGROUND: The study aimed to define the frequencies of type 1 diabetes-associated gene polymorphisms and their associations with various diabetes-associated autoantibodies in Egyptian children. METHODS: One hundred and one children with type 1 diabetes and 160 healthy controls from the same region were studied for HLA-DQB1, HLA-DQA1, and HLA-DRB1 (DR4 subtypes) alleles; for INS and protein tyrosine phosphatase, non-receptor type 22 gene polymorphisms (rs689 and rs2476601); and for diabetes-associated autoantibodies. RESULTS: Most children with diabetes (77.2%) were positive for the HLA-(DR3)-DQA1*05-DQB1*02 (DR3-DQ2) haplotype compared with 26.2% of the controls (OR = 9.5; p < 0.001). HLA-DRB1*04:02-DQA1*03-DQB1*03:02 (DR4-DQ8) (26.7%, OR = 3.3; p < 0.001), DRB1*04:05-DQA1*03-DQB1*02 (DR4-DQ2) (23.8%, OR 5.2; p < 0.001), and DRB1*04:05-DQA1*03-DQB1*03:02 (DR4-DQ8) (8.9%, OR = 7.7; p = 0.007) were also significantly increased. HLA-(DR15)-DQB1*06:01, (DR13)-DQB1*06:03, and DRB1*04:03-DQA1*03-DQB1*03:02 were the most protective haplotypes with OR values from 0.04 to 0.06. Patients positive for DR3-DQ2 but negative for DR4 haplotypes had a high frequency of glutamic acid decarboxylase antibodies (78%; p < 0.001 versus other genotypes), but only 26.6% of those with DR3-DQ2/DR4-DQ2 tested positive for glutamic acid decarboxylase antibodies (p = 0.006 versus other genotypes). Subjects with the DR4-DQ8 haplotype without DR3-DQ2 or DR4-DQ2 were more often positive for islet antigen-2 and zinc transporter 8 antibodies (55.5%, p = 0.007 and 55.5%, p = 0.01 respectively). The AA genotype of the INS gene was more common in patients than in controls (75.2 versus 59.5%, OR = 2.07; p = 0.018). CONCLUSIONS: Besides a strong HLA-DR3-DQ2 association, a relatively high frequency of the DR4-DQ2 haplotype characterized the diabetic population. The low frequency of autoantibodies in children with HLA-DR4-DQ2 may indicate specific pathogenetic pathways associated with this haplotype.

A New Look on Adding Dexamethasone as an Adjuvant to Caudal Bupivacaine; Efficacy on Postoperative Pain and Vomiting in Pediatric Patients.

BACKGROUND: Controlling postoperative pain and vomiting in children remains a great challenge. OBJECTIVE: Study the efficacy of adding dexamethasone to caudal bupivacaine on postoperative analgesia and vomiting. STUDY DESIGN: Prospective, randomized double blind controlled clinical trial. SETTING: Assiut University Hospital. PATIENTS: Ninety children ASA I-II, undergoing lower orthopedic surgeries. METHODS: Patients were randomly allocated into 3 equal groups. All received caudal block after induction of anesthesia with 0.5 mL/kg of 0.25% bupivacaine in addition to 5 mL intravenous (IV) normal saline in the control group, IV 0.5 mg/kg dexamethasone in IV dexamethasone group and lastly 0.1 mg/kg dexamethasone in the caudal dexamethasone group. Postoperative pain scores and rescue analgesic consumption were recorded. Blood glucose, postoperative vomiting, and other side effects were evaluated up to 24 hours after extubation. RESULTS: The time of first analgesia and the number of patients requiring rescue analgesics were significantly decreased with intravenous or caudal dexamethasone. No significant increase in postoperative blood glucose levels were observed. A significant increase in B- Endorphin level at 3 and 24 hours postoperative was found in both dexamethasone groups when compared with the preoperative baseline value. The incidence of postoperative vomiting was significantly decreased in both dexamethasone groups in comparison with the control group. No other side effects were detected. LIMITATIONS: Measurement of serum cortisol. CONCLUSION: Analgesic and antiemetic effects of dexamethasone as an adjunct to caudal block with bupivacaine (0.25%) 0.5 mL/kg is similar whether administered intravenously 0.5 mg/kg or caudally 0.1 mg/kg.