9The TANTALUSTM System for obesity: effect on gastric emptying of solids

Background: Gastric electrical stimulation (GES) is currently investigated for the treatment of obesity. The TANTALUS System delivers gastric contractility modulation (GCM) signals in synchrony with gastric slow waves, resulting in significant augmentation of gastric contractions during food intake. We hypothesized that such modulation of contractile activity may affect gastric emptying and plasma ghrelin levels. Aim: To test the effect of GCM of the gastric antrum on gastric emptying of solids and ghrelin levels. Methods: 12 obese subjects were implanted with 2 pairs of antral electrodes and an implantable pulse generator (IPG, TANTALUS ^TM) Gastric emptying test (GE) for solids was performed twice, on separate days, in each subject, starting few weeks after implantation: 1) control, before the start of stimulation, and 2) with stimulation, after device was turned on. Blood samples for ghrelin, were taken at baseline, and at 15, 30, 60 and 120 min after the test meal. Results as mean + SD, analysis by t‐test and p < 0.05. Results: 11 females, 1 male, age: 39.1 ± 8.9 years, BMI: 41.6 ± 3.4, 3 subjects with type 2 diabetes. One diabetic patient did not complete GE test because of technical issues. GCM significantly accelerated gastric emptying: retention at 2 hours 18.7 ± 12.2% vs. 31.9 ± 16.4%, stimulation vs. control respectively, p = 0.008. T ^1/2 78.3 ± 23.5 vs. 95 ± 31.7 min, stimulation vs. control respectively, p = 0.04. Mean results for gastric emptying were within normal at both baseline and stimulation. Meal ingestion induced only minimal, insignificant reduction in ghrelin levels. There was no significant difference in AUC of ghrelin between control and stimulation. Conclusions: After GCM stimulation, there is significant acceleration of gastric emptying of solids in obese patients, without affect on ghrelin levels. The obese subjects did not exhibit the significant, meal‐induced reduction in ghrelin.      

Evaluation of postpartum blood loss after misoprostol-induced labour

Objective  To objectively evaluate postpartum blood loss after successful misoprostol induction and compare it with blood loss after oxytocin induction of labour.
Design  Prospective randomised study.
Setting  Labour ward in university maternity hospital.
Population  A total of 150 women up to third parity with completed 40 weeks of singleton normal pregnancy, average size cephalic fetus.
Methods  Cases were randomised between oxytocin induction and misoprostol induction. Blood was collected in suction set and measured in the delivery room starting after delivery of the fetus and was evaluated by pad weighing in the following 6 hours. Pre- and postdelivery haematocrit were measured and difference between the two values was assessed and analysed.
Main outcome measures  Success of induction, induction delivery interval, postpartum blood loss, and difference between pre- and postdelivery haematocrit.
Results  Induced labour was significantly faster with misoprostol induction ( P < 0.001). Blood loss and haematocrit difference was significantly greater in the misoprostol group than in oxytocin group ( P < 0.02 and 0.001, respectively). Blood loss in both groups was significantly correlated with higher initial Bishop score ( P < 0.001 and 0.024, respectively) and short labour duration ( P < 0.0002 and 0.0001, respectively).
Conclusions  Misoprostol induction is associated with increased blood loss especially when used in women with high Bishop score; therefore, it is better reserved for cases requiring cervical ripening.     

Is MSH2 a breast cancer susceptibility gene?

Mutations in the DNA mismatch repair gene MSH2 lead to increased replication error and microsatellite instability and account for a substantial proportion of hereditary non-polyposis colorectal cancer (Lynch syndrome). A recent international collaborative genome-wide linkage scan (GWS) for breast cancer susceptibility loci found some evidence for there being a breast cancer susceptibility gene in a genomic region on chromosome 2p close to MSH2. We sought to investigate the possibility that mutations in MSH2 might explain the multiple cases of breast cancer in some families that were included in the international GWS. DNA samples from the affected probands of 59 multiple-case breast cancer families, many of whom gave LOD scores >0.5 in the MSH2 region, were screened for large genomic alterations in MSH2 via the Multiplex Ligation-dependant Probe Amplification (MLPA) assay and for coding region mutations via exonic sequencing. Several of the families also contained cases of colorectal cancer in addition to breast cancer and had been included in the GWS that had identified a positive LOD score on chromosome 2p. Using MLPA, c.1236C > T was identified in one proband but this variant was not predicted to create an alternate acceptor/donor site within exon 7 MSH2 using in silico analyses. A c.1734T > C was identified in a second proband via exonic sequencing but testing of the variant in other family members did not support segregation of this variant with disease. Extensive screening of 59 multiple-case breast cancer families did not identify any coding region mutations or larger genomic alterations in MSH2 that might implicate MSH2 as a breast cancer susceptibility gene.     

BK virus nephropathy in a pediatric patient after hematopoietic stem cell transplantation

We report the case of a seven‐yr‐old Caucasian girl who presented with progressive deterioration of renal function 13 months after HSCT for myelodysplastic syndrome. BK virus nephropathy was suspected and confirmed. After reduction of immunosuppression and treatment with IVIG, leflunomide, ciprofloxacin, and cidofovir, clearance of BK virus from blood was achieved, and further progression or renal failure was prevented. We believe that BK virus nephropathy should be considered in cases of renal function deterioration in all immunocompromised patients.     

Cyclosporin-A nephrotoxicity and acute cellular rejection in renal transplant recipients: correlation between radionuclide and histologic findings

Serial radionuclide studies using both Tc-99m DTPA (perfusion) and I-131 hippuran (tubular function) were correlated with histologic findings in 25 patients with renal transplants. These cases included 15 cases of cyclosporin-A nephrotoxicity (CsA-NT) and ten cases of acute cellular rejection that were retrospectively selected on the basis of biopsy findings and favorable clinical response to therapy specific for each of these conditions. The serial radionuclide studies enabled the correct diagnosis in 12 of 15 cases of CsA-NT and eight of ten cases of acute rejection. Posttherapy radionuclide studies, furthermore, demonstrated improvement consistent with clinical response. In all cases, the radionuclide results were available at least 24 hours before biopsy findings. These results indicate that serial radionuclide studies evaluating interval changes in both perfusion and tubular function are of significant value in the diagnosis and follow-up of CsA-NT and acute cellular rejection in transplant recipients. This initial experience suggests a sensitivity of 80%.     

15The effect of Lower Esophageal Sphincter (LES) electrical stimulation on LES pressure

Background: Electrical stimulation (ES) of the stomach has been shown to modulate LESP. Electrical stimulation, using neural high frequency stimulation (NGES) can induce contractions of the smooth muscle of the gut. The purpose of this study was to determine if electrical stimulation of the LES can affect LESP. Methods: Four female hound dogs, weight: 20–25 kg, underwent an esophagostomy that allowed the introduction of a sleeve manometry catheter into the esophagus. They were also implanted with a pair of electrodes along the longitudinal axis of the LES. After 3 weeks of recovery, they underwent esophageal manometry recording during control and ES, performed randomly on separate days, using 4 different stimulations: 1‐Low frequency: freq: 6 cycles/min, pulse: 350 milisec, amp: 5 mAmp; 2 High‐frequency: freq: 50 Hz, pulse: 1 milisec, amp: 5 mAmp; 3‐ NGES: freq: 50 Hz, pulse:20 milisec, amp:10 volts; 4‐ High‐frequency, circular: freq: 20 Hz, pulse:1 milisec, amp:5 mAmp. All recordings were performed 1 hour after consumption of 3 ounces of canned dog food, to prevent fluctuations in LESP and under mild sedation (acepromazine 0.5 mg kg^­1). Tests consisted, during ES days, of 3 periods of 20 minutes each: control , stimulation and post stimulation. The effect of NGES was also tested under anesthesia and following administration of L‐NAME 50 mg kg^­1 IV. and also atropine 0.05 mg kg^­1 IV. Analysis: area under the curve (AUC) and pressure were compared among the 3 periods. Data shown as mean ± SD, ANOVA and t‐test, p < 0.05. Results: Sustained increase in LESP was observed during low frequency stimulation, 32.1 ± 12.8 vs. 42.4 ± 18.0 vs. 50.1 ± 23.6, control vs. stimulation vs. post stimulation respectively, p = 0.013. AUC also significantly increased during and after stimulation, 39,320.3 ± 15,722 vs. 51,294 ± 21,826 vs. 59,823.6 ± 28,198.4 mmHgxsec, control vs. stimulation vs. post stimulation respectively, p = 0.01. There was no significant change with other types of ES. NGES induced an initial rise in LESP followed within few seconds by relaxation with slow resumption of pressure over a 1 minute period. L‐NAME increased LESP and augmented the initial rise in LESP following NGES but markedly diminished or abolished the relaxation phase. Atropine lowered LESP and abolished the initial rise in LESP induced by NGES. Conclusions: Low frequency ES of the LES increases LESP in conscious dogs. NGES has dual effect on LESP: an initial stimulation, cholinergically mediated, followed by relaxation mediated by nitric oxide.