Hyperactive hypothalamus, motivated and non-distractible chronic overeating in ADAR2 transgenic mice.

ADAR2 transgenic mice misexpressing the RNA editing enzyme ADAR2 (Adenosine Deaminase that act on RNA) show characteristics of overeating and experience adult onset obesity. Behavioral patterns and brain changes related to a possible addictive overeating in these transgenic mice were explored as transgenic mice display chronic hyperphagia. ADAR2 transgenic mice were assessed in their food preference and motivation to overeat in a competing reward environment with ad lib access to a running wheel and food. Metabolic activity of brain and peripheral tissue were assessed with [(18) F] fluorodeoxyglucose positron emission tomography (FDG-PET) and RNA expression of feeding related genes, ADAR2, dopamine and opiate receptors from the hypothalamus and striatum were examined. The results indicate that ADAR2 transgenic mice exhibit, (1) a food preference for diets with higher fat content, (2) significantly increased food intake that is non-distractible in a competing reward environment, (3) significantly increased messenger RNA (mRNA) expressions of ADAR2, serotonin 2C receptor (5HT2C R), D1, D2 and mu opioid receptors and no change in corticotropin-releasing hormone mRNAs and significantly reduced ADAR2 protein expression in the hypothalamus, (4) significantly increased D1 receptor and altered bioamines with no change in ADAR2, mu opioid and D2 receptor mRNA expression in the striatum and (5) significantly greater glucose metabolism in the hypothalamus, brain stem, right hippocampus, left and right mid brain regions and suprascapular peripheral tissue than controls. These results suggest that highly motivated and goal-oriented overeating behaviors of ADAR2 transgenic mice are associated with altered feeding, reward-related mRNAs and hyperactive brain mesolimbic region.

Neonatal jaundice--are we over-treating?

Hyperbilirubinaemia is the most common condition requiring evaluation and treatment in newborns. A study in the NEJM 2006 suggested that current guidelines for the treatment of hyperbilirubinaemia in otherwise healthy infants should be relaxed. Prompted by this we performed a retrospective review of review of all term infants who received phototherapy between 1998 and 2006 (total number births = 56,894) in the National Maternity Hospital, Holles Street. 1441 infants received phototherapy during this time period (2.5%). Of those that were of term gestation (n=539), only 9% of those infants receiving phototherapy had peak total serum bilirubin (TSB) exceeding 400 umol. Twenty six percent of infants who received phototherapy had a peak TSB that never exceeded 250 umol/l. There were no cases of kernicterus. Review of the Coombs status revealed that 27% of those undergoing phototherapy in the lowest TSB range were Coombs positive. Seven Coombs positive infants had peak TSB >400 umol/l (14%). Four Coombs positive infants received exchange transfusions. Following this study we would concur with the opinion of Newman et al that current guidelines for the treatment of hyperbilirubinaemia in otherwise healthy infants could be relaxed.

Efficacy of intravenous immunoglobulin in the management of haemolytic disease of the newborn.

Intravenous immunoglobulin (IVIG) is indicated for use in Rhesus and ABO hemolytic disease of the newborn (HDN) to reduce the need for exchange transfusion, to decrease hospital stay and the duration of phototherapy. 11 infants received IVIG and the effect of IVIG on the total serum bilirubin (TSB) level, and its effect on the rate of rise of TSB was quantified. There was a statistically significant decrease in bilirubin levels before and after treatment with IVIG from 234 to 219 micromol/L (p = 0.001). In addition, the rate of change in bilirubin level significantly altered from an upward to a downward trend. (p = 0.001). The Number Needed to Treat (NNT) to prevent an exchange transfusion was 2.75--comparable with the recent systematic review of IVIG with a NNT of 2.7.

Pursed lips breathing improves ventilation in myotonic muscular dystrophy.

OBJECTIVE: To determine the effects of pursed lips breathing on ventilation, chest wall mechanics, and abdominal muscle recruitment in myotonic muscular dystrophy (MMD). DESIGN: Before-after trial. SETTING: University hospital pulmonary function laboratory. PARTICIPANTS: Eleven subjects with MMD and 13 normal controls. INTERVENTION: Pursed lips breathing. OUTCOME MEASURES: Electromyographic (EMG) activity of the transversus abdominis, external oblique, internal oblique, and rectus abdominis was recorded with simultaneous measures of gastric pressure, abdominal plethysmography, and oxygen saturation. Self-reported sensations of dyspnea, respiratory effort, and fatigue were recorded at the end of each trial. RESULTS: Pursed lips breathing and deep breathing led to increased tidal volume, increased minute ventilation, increased oxygen saturation, reduced respiratory rate, and reduced endexpiratory lung volume. Dyspnea, respiratory effort, and fatigue increased slightly with pursed lips breathing. EMG activity of the transversus abdominis and internal oblique muscles increased in MMD only and was associated with an increase in gastric pressure. CONCLUSIONS: Pursed lips breathing and deep breathing are effective and easily employed strategies that significantly improve tidal volume and oxygen saturation in subjects with MMD. Abdominal muscle recruitment does not explain the ventilatory improvements, but reduced end-expiratory lung volume may increase the elastic recoil of the chest wall. Further clinical studies are needed to ascertain if the ventilatory improvements with pursed lips breathing and deep breathing improve pulmonary outcomes in MMD.