HLA Genes, Islet Autoantibodies and Residual C-Peptide at the Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years Later

HLA genes, islet autoantibodies and residual C-peptide were studied to determine the independent association of each exposure with diabetic retinopathy (DR), 15 years after the clinical onset of type 1 diabetes in 15-34 year old individuals.The cohort was identified in 1992 and 1993 by the Diabetes Incidence Study in Sweden (DISS), which investigates incident cases of diabetes for patients between 15 and 34 years of age. Blood samples at diagnosis were analyzed to determine HLA genotype, islet autoantibodies and serum C-peptide. In 2009, fundus photographs were obtained from patient records. Study measures were supplemented with data from the Swedish National Diabetes Registry.The prevalence of DR was 60.2% (148/246). Autoantibodies against the 65 kD isoform of glutamate decarboxylase (GADA) at the onset of clinical diabetes increased the risk of DR 15 years later, relative risk 1.12 for each 100 WHO units/ml, [95% CI 1.02 to 1.23]. This equates to risk estimates of 1.27, [95% CI 1.04 to 1.62] and 1.43, [95% CI 1.06 to 1.94] for participants in the highest 25(th) (GADA>233 WHO units/ml) and 5(th) percentile (GADA>319 WHO units/ml) of GADA, respectively. These were adjusted for duration of diabetes, HbA(1c), treated hypertension, sex, age at diagnosis, HLA and C-peptide. Islet cell autoantibodies, insulinoma-antigen 2 autoantibodies, residual C-peptide and the type 1 diabetes associated haplotypes DQ2, DQ8 and DQ6 were not associated with DR.Increased levels of GADA at the onset of type 1 diabetes were associated with DR 15 years later. These results, if confirmed, could provide additional insights into the pathogenesis of the most common microvascular complication of diabetes and lead to better risk stratification for both patient screenings and DR treatment trials

Use of Gabapentin for Perioperative Pain Control – a Meta-Analysis

BACKGROUND: Gabapentin, an anticonvulsant, has recently been suggested as an effective postoperative ‘analgesic’ agent. The objective of the present study was to examine the analgesic effectiveness, opioid-sparing effects and side effects associated with the use of gabapentin in a perioperative setting.METHODS: Following the Quality of Reporting of Meta-analyses recommendations, nine electronic databases until February 2006 were searched, without language restriction, for randomized controlled trials comparing gabapentin with control for postoperative pain control. Outcome measures, namely, 24 h cumulative opioid consumption, visual analogue scale pain scores and adverse effects, were expressed as odds ratios, ratio of means or weighted mean differences (as appropriate), which were aggregated under the fixed or random effects models.RESULTS: Gabapentin caused a 35% reduction in total opioid consumption over the first 24 h following surgery (ratio of means 0.65, 95% CI 0.59 to 0.72), a significant reduction in postoperative pain at rest (in the first 24 h) and with movement (at 2 h, 4 h and 12 h), regardless of whether treatment effects were expressed as ratios of means or weighted mean differences, and a reduction of vomiting (relative risk [RR] 0.73, 95% CI 0.56 to 0.95) and pruritus (RR 0.30, 95% CI 0.13 to 0.70). It was associated with a significant increase in dizziness (RR 1.40, 95% CI 1.06 to 1.84) and an increase in sedation of borderline significance (RR 1.65, 95% CI 1.00 to 2.74).CONCLUSION: Gabapentin improves the analgesic efficacy of opioids both at rest and with movement, reduces analgesic consumption and opioid-related adverse effects, but is associated with an increased incidence of sedation and dizziness.Peer Reviewe

Use of gabapentin for perioperative pain control – A meta-analysis

BACKGROUND: Gabapentin, an anticonvulsant, has recently been suggested as an effective postoperative ‘analgesic’ agent. The objective of the present study was to examine the analgesic effectiveness, opioid-sparing effects and side effects associated with the use of gabapentin in a perioperative setting

The role of inflammation in perinatal brain injury

Inflammation is increasingly recognized as being a critical contributor to both normal development and injury outcome in the immature brain. The focus of this Review is to highlight important differences in innate and adaptive immunity in immature versus adult brain, which support the notion that the consequences of inflammation will be entirely different depending on context and stage of CNS development. Perinatal brain injury can result from neonatal encephalopathy and perinatal arterial ischaemic stroke, usually at term, but also in preterm infants. Inflammation occurs before, during and after brain injury at term, and modulates vulnerability to and development of brain injury. Preterm birth, on the other hand, is often a result of exposure to inflammation at a very early developmental phase, which affects the brain not only during fetal life, but also over a protracted period of postnatal life in a neonatal intensive care setting, influencing critical phases of myelination and cortical plasticity. Neuroinflammation during the perinatal period can increase the risk of neurological and neuropsychiatric disease throughout childhood and adulthood, and is, therefore, of concern to the broader group of physicians who care for these individuals