Human Placental LRP5 and Sclerostin are Increased in Gestational Diabetes Mellitus Pregnancies.

INTRODUCTION: The low-density lipoprotein receptor-related protein 5 (LRP5) and its inhibitor sclerostin, are key components of bone metabolism and potential contributors to type 2 diabetes mellitus susceptibility. This study aims at evaluating the expression of placental LRP5 and sclerostin in pregnancies with gestational diabetes mellitus (GDM) and investigate possible associations with umbilical sclerostin concentrations and clinical outcomes in mothers and their neonates. METHODS: Twenty-six GDM-mothers and 34 non-GDM mothers of Caucasian origin and their neonates admitted in a gynecology and obstetrics department of a university hospital were included in this study. Demographic data and maternal fasting glucose concentrations (24-28 weeks of gestation) were retrieved from the patients' medical records. Placental LRP5 was determined by immunohistochemistry (IHC) and Western blotting analysis; placental sclerostin was determined by IHC. Umbilical serum sclerostin concentrations were measured by ELISA. RESULTS: Placental sclerostin IHC intensity values were positively correlated with LRP5 values as detected either by IHC (r = 0.529; P < .001) or Western blotting (r = 0.398; P = .008), with pregestational maternal body mass index values (r = 0.299; P = .043) and with maternal fasting glucose concentrations (r = 0.475; P = .009). Placental sclerostin and LRP5 were significantly greater in GDM compared with non-GDM placentas (histo-score: 65.08 ± 17.09 vs 11.45 ± 2.33, P < .001; 145.53 ± 43.74 vs 202.88 ± 58.65, P < .001; respectively). DISCUSSION: Sclerostin and LRP5 were detected in human placentas. The overexpression of placental sclerostin and LRP5 values in GDM compared with non-GDM pregnancies, as well as the positive association of placental sclerostin values with pregestational maternal body mass index and maternal fasting glucose concentrations may indicate the development of an adaptive mechanism in face of maternal hyperglycemia.

Redo antireflux surgery--the importance of a tailored approach.

OBJECTIVE: Although several studies have examined early outcome following redo antireflux surgery, there is little data on the long-term efficacy of these procedures. We reviewed our experience of these operations in order to assess the long-term results which can be achieved by choosing redo antireflux procedures based on the results obtained from pre-operative oesophageal function testing. METHODS: The case notes of 26 patients who underwent a repeat antireflux procedure between 1981 and 2000 were reviewed. Clinical history, examination, endoscopy, pH studies, oesophageal manometry and video barium contrast studies were performed on all patients prior to re-operation. In all cases, a standardised pre-formulated algorithm, based on the results of the pre-operative oesophageal function tests, was used to determine the choice of surgical procedure. Post-operatively, patients were classified into three groups: Group A (those with no symptoms), Group B (symptoms controlled by medication) and Group C (symptoms refractory to medical treatment). Patients in Groups B and C underwent repeat oesophageal function studies. RESULTS: In all cases, the indication for re-operation was gastro-oesophageal reflux symptoms refractory to medical treatment. Twenty-one patients (81%) underwent a left thoracotomy, of whom 11 patients (42%) underwent a gastroplasty. The mean follow-up period was 8.27 years (range 1.5-19.8 years), after which 14 patients (54%) were classified as Group A; 10 patients (38%) as Group B; and 2 patients (8%) as Group C. Within Groups B and C, manometry showed that re-operation had increased basal lower oesophageal sphincter pressure (4.6 vs 12.7 mmHg, pre- vs post-operative P=0.03), and in all, but one case pH studies showed no evidence of recurrent acid reflux. CONCLUSIONS: Redo antireflux surgery can provide complete symptomatic relief in approximately 50% of patients and symptomatic improvement over 90% of patients. We advocate a tailored approach in the selection of re-operative procedures based on the results of pre-operative oesophageal function testing.