J. Toouli

Change in liver size and fat content after treatment with Optifast Very Low Calorie Diet

Background: Laparoscopic adjustable gastric banding (LAGB) requires surgical access to the gastroesophageal junction, which may be compromised by the enlarged, fatty liver that is frequently encountered in the obese. Liver size appears reduced and surgical access improved following preoperative weight loss with Optifast® Very Low Calorie Diet (VLCD). The aim of this study was to assess the effects of 6 weeks Optifast® VLCD on liver volume and fat content. Methods: 18 morbidly obese subjects underwent magnetic resonance imaging and spectroscopy to measure liver size and fat content before and after intensive treatment with Optifast® VLCD for 6 weeks. Results: All subjects completing 6 weeks Optifast® VLCD lost weight. Body weight and BMI (median [interquartile range]) reduced from 119.7 [111.9-131.3] kg and 44 [40-51] kg/m2 respectively, to 110.6 [98.0124.5] kg and 40 [36-47] kg/m2, P<0.001. Median excess weight loss (EWL) was 15.1 [9.6-21.1]%. Baseline liver volume and fat content were related (r=0.633, P=0.005). After 6 weeks Optifast® VLCD, there was a 14.7% reduction in mean liver volume (P<0.001) and a 43% reduction in mean liver fat (P=0.016). The change in liver volume was predicted by the change in the liver fat (r = 0.610, P=0.012). Conclusion: This study has demonstrated that a 6week diet with Optifast® VLCD results in significant related reductions in liver size and liver fat content. This suggests that the reduction in liver volume is due to loss of fat. The reduction in liver fat and volume likely accounts for the perceived improved operability in patients undergoing LAGB.

Intra-abdominal vagal blocking (VBLOC therapy): Clinical results with a new implantable medical device

BACKGROUNDnA new medical device uses high-frequency electrical algorithms to create intermittent vagal blocking (VBLOC therapy). The aim is to assess the effects of vagal blocking on excess weight loss (EWL), safety, dietary intake, and vagal function.nnnMETHODSnAn open-label, 3-center study was conducted in obese subjects (body mass index [BMI] 35-50 kg/m(2)). Electrodes were implanted laparoscopically on both vagi near the esophagogastric junction to provide electrical block. Patients were followed for 6 months for body weight, safety, electrocardiogram, dietary intake, satiation, satiety, and plasma pancreatic polypeptide (PP) response to sham feeding. To specifically assess device effects alone, no diet or exercise programs were instituted.nnnRESULTSnThirty-one patients (mean BMI, 41.2 +/- 1.4 kg/m(2)) received the device. Mean EWL at 4 and 12 weeks and 6 months after implant was 7.5%, 11.6%, and 14.2%, respectively (all P < .001); 25% of patients lost >25% EWL at 6 months (maximum, 36.8%). There were no deaths or device-related serious adverse events (AEs). Calorie intake decreased by >30% at 4 and 12 weeks and 6 months (all P <or= .01), with earlier satiation (P < .001) and reduced hunger (P = .005). After 12 weeks, plasma PP responses were suppressed (20 +/- 7 vs 42 +/- 19 pg/mL). Average percent EWL in patients with PP response <25 pg/mL was double that with PP response >25 pg/mL (P = .02). Three patients had serious AEs that required brief hospitalization, 1 each for lower respiratory tract, subcutaneous implant site seroma, and Clostridium difficile diarrhea.nnnCONCLUSIONSnIntermittent, intra-abdominal vagal blocking is associated with significant EWL and a desirable safety profile.

Functional disorders of the biliary tract and pancreas

The term “dysfunction” defines the motor disorders of the gall bladder and the sphincter of Oddi (SO) without note of the potential etiologic factors for the difficulty to differentiate purely functional alterations from subtle structural changes. Dysfunction of the gall bladder and/or SO produces similar patterns of biliopancreatic pain and SO dysfunction may occur in the presence of the gall bladder. The symptom-based diagnostic criteria of gall bladder and SO dysfunction are episodes of severe steady pain located in the epigastrium and right upper abdominal quadrant which last at least 30 minutes. Gall bladder and SO dysfunctions can cause significant clinical symptoms but do not explain many instances of biliopancreatic type of pain. The syndrome of functional abdominal pain should be differentiated from gall bladder and SO dysfunction. In the diagnostic workup, invasive investigations should be performed only in the presence of compelling clinical evidence and after non-invasive testing has yielded negative findings. Gall bladder dysfunction is suspected when laboratory, ultrasonographic, and microscopic bile examination have excluded the presence of gallstones and other structural abnormalities. The finding of decreased gall bladder emptying at cholecystokinin-cholescintigraphy is the only objective characteristic of gall bladder dysfunction. Symptomatic manifestation of SO dysfunction may be accompanied by features of biliary obstruction (biliary-type SO dysfunction) or significant elevation of pancreatic enzymes and pancreatitis (pancreatic-type SO dysfunction). Biliary-type SO dysfunction occurs more frequently in postcholecystectomy patients who are categorized into three types. Types I and II, but not type III, have biochemical and cholangiographic features of biliary obstruction. Pancreatic-type SO dysfunction is less well classified into types. When non-invasive investigations and endoscopic retrograde cholangiopanreatography show no structural abnormality, manometry of both biliary and pancreatic sphincter may be considered.

Vagal Blocking Improves Glycemic Control and Elevated Blood Pressure in Obese Subjects with Type 2 Diabetes Mellitus

Background. An active device that downregulates abdominal vagal signalling has resulted in significant weight loss in feasibility studies. Objective. To prospectively evaluate the effect of intermittent vagal blocking (VBLOC) on weight loss, glycemic control, and blood pressure (BP) in obese subjects with DM2. Methods. Twenty-eight subjects were implanted with a VBLOC device (Maestro Rechargeable System) at 5 centers in an open-label study. Effects on weight loss, HbA1c, fasting blood glucose, and BP were evaluated at 1 week to 12 months. Results. 26 subjects (17 females/9 males, 51 ± 2 years, BMI 37 ± 1u2009kg/m2, meanu2009±u2009SEM) completed 12 months followup. One serious adverse event (pain at implant site) was easily resolved. At 1 week and 12 months, mean excess weight loss percentages (% EWL) were 9 ± 1% and 25 ± 4% (P < 0.0001), and HbA1c declined by 0.3 ± 0.1% and 1.0 ± 0.2% (P = 0.02, baseline 7.8 ± 0.2%). In DM2 subjects with elevated BP (n = 15), mean arterial pressure reduced by 7 ± 3u2009mmHg and 8 ± 3u2009mmHg (P = 0.04, baseline 100 ± 2u2009mmHg) at 1 week and 12 months. All subjects MAP decreased by 3 ± 2u2009mmHg (baseline 95 ± 2u2009mmHg) at 12 months. Conclusions. VBLOC was safe in obese DM2 subjects and associated with meaningful weight loss, early and sustained improvements in HbA1c, and reductions in BP in hypertensive DM2 subjects. This trial is registered with ClinicalTrials.gov NCT00555958.

The Early Effects of Weight Loss Surgery on Regional Adiposity

Background: Weight loss beyond 6 months following laparoscopic adjustable gastric banding (LAGB) is associated with a preferential mobilization of visceral adipose tissue and an improvement in insulin sensitivity in insulin resistant subjects. Because the rate of weight loss is greatest in the first 3 months after LAGB, we investigated the impact of LAGB on changes in regional lipid deposition and insulin sensitivity over this period. Methods: 10 female obese non-diabetic subjects underwent magnetic resonance (MR) imaging and spectroscopy before and 12 weeks after LAGB (using the Swedish band), for the quantification of abdominal subcutaneous and visceral adipose tissue areas and intrahepatic lipid. Fasting blood free fatty acids were analyzed. Insulin sensitivity was monitored by fasting insulin and homeostasis model assessment (HOMA). Results: Median weight loss 12 weeks after gastric banding was 9.5 kg [interquartile range (IQR): −16.5 to −6]. There were significant reductions in median abdominal subcutaneous (−20% [IQR: −24 to −13]) and visceral (−15% [IQR: −49 to −8]) adipose tissue depots as well as plasma free fatty acids (−34% [IQR: −79 to −8]). The amount of weight lost was directly proportional to the initial BMI (r=0.778; P=0.008). Visceral fat loss was proportional to initial visceral adiposity (r=0.80, P=0.01). There was no significant improvement in insulin sensitivity. Conclusion: Significant fat loss occurs 3 months after LAGB. The absence of a concurrent improvement in insulin sensitivity may reflect the relatively small reduction in visceral adipose tissue at this stage. Improvement in insulin sensitivity beyond 3 months after LAGB may be due to the continued loss of visceral adipose tissue.

Distribution of nitric oxide synthase and vasoactive intestinal polypeptide immunoreactivity in the sphincter of Oddi and duodenum of the possum.

Abstract. The nitrergic innervation of the sphincter of Oddi (SO) and duodenum in the Australian brush-tailed possum and the possible association of this innervation with the neuropeptide vasoactive intestinal polypeptide (VIP) were investigated by using immunohistochemical localisation of nitric oxide synthase (NOS) and VIP, together with the general neuronal marker, protein gene product 9.5 (PGP9.5). Whole-mount preparations of the duodenum and attached SO without the mucosa, submucosa and circular muscle (n=12) were double- and triple-labelled. The density of myenteric nerve cell bodies of the SO in the more distal region (duodenal end) was significantly higher than that in the more proximal region. In the SO, approximately 50% of all cells were NOS-immunoreactive (IR), with 27% of the NOS-IR cells being VIP-IR. Within the duodenal myenteric plexus, NOS immunoreactivity was present in about 25% of all neurons, with 27% of these NOS-IR neurons also being VIP-IR, a similar proportion to that in the SO. Varicose nerve fibres with NOS and VIP immunoreactivity were present within the myenteric and submucous plexuses of the SO and duodenum, and in the circular and longitudinal muscle layers. The NOS-positive cells within both the SO and duodenum were unipolar, displaying a typical Dogiel typexa0I morphology. The myenteric plexuses of the SO and duodenum were in direct continuity, with many interconnecting nerve trunks, some of which showed NOS and VIP immunoreactivity. Thus, the possum possesses an extensive NOS innervation of the SO and duodenum, with a significantly higher proportion of NOS-IR neurons within the SO, a subset of which contains VIP.

Galanin receptor 3 – a potential target for acute pancreatitis therapy

Backgroundu2002 Galanin participates in the pathogenesis of acute pancreatitis (AP). The galanin receptor (GALR) sub‐types involved, however, are unclear. We aimed to determine GALRs messenger RNA (mRNA) expression in mouse pancreas, describe their localization, and ascertain if GALR2 and GALR3 are involved in AP.

Abdominal adiposity and liver fat content 3 and 12 months after gastric banding surgery

Weight loss after laparoscopic adjustable gastric banding surgery (LAGB) is associated with mobilization of adipose tissue from a variety of depots. We sought to evaluate and relate abdominal and hepatic lipid deposition in an obese female population 3 and 12 months after LAGB. We related changes in these depots to markers of insulin sensitivity. Eighteen female obese subjects underwent magnetic resonance imaging and spectroscopy before and 3 and 12 months after LAGB for the quantification of abdominal subcutaneous (ABSAT) and visceral (VAT) adipose tissue areas and liver fat content (LFAT). Fasting blood free fatty acids (FFA) were analyzed. Insulin sensitivity was assessed by the homeostasis model assessment of insulin resistance index (HOMA-R). Mean weight loss 3 and 12 months after LAGB was 9.8 +/- 1.1 kg and 20.0 +/- 2.2 kg, respectively. Postoperatively, VAT area loss exceeded ABSAT area loss in the cohort as a whole and when divided according to preoperative liver fat stores. Three months after LAGB, reductions had occurred in VAT and ABSAT areas (both P < .01) and in FFA (P < .05). Twelve months after LAGB, further significant reductions (P < .01) occurred in VAT and ABSAT areas but not in FFA. No significant reduction occurred in LFAT at either time point in the group as a whole. In those with preoperative hepatic steatosis (LFAT > approximately 5%, n = 7), LFAT fell by 42% (P = .036) 3 months after LAGB, with a total reduction of 50% (P = .027 cf baseline) occurring by 12 months. There was an improvement in HOMA-R at 12 months (1.9 +/- 0.3 cf 2.9 +/- 0.5 at baseline, P = .04) but not 3 months (2.7 +/- 0.4). Preoperatively, LFAT related significantly to VAT area (r = 0.67, P = .003) and HOMA-R (r = 0.497, P = .04) but not ABSAT area. Postoperatively at both 3 and 12 months, LFAT continued to relate to VAT area (r = 0.63, P < .01 at both time points) but not HOMA-R. The changes in LFAT and VAT area were unrelated postoperatively. Abdominal adipose tissue loss was greater from the visceral than subcutaneous depots, suggesting that insulin sensitivity may not be an important determinant of selective lipid depot loss. The lack of a significant change in liver fat in the group as a whole may relate to low preoperative liver fat stores and to high postoperative dietary fat intakes. Preoperative liver fat stores did not influence insulin sensitivity or abdominal lipid changes during weight loss. Liver fat content and VAT area interrelated more closely than either related to ABSAT area, suggesting differing regulatory pathways for fat mobilization from ABSAT and VAT depots but possibly similar pathways for storage and mobilization of fat in the liver and viscerally.

Associates of change in liver fat content in the morbidly obese after laparoscopic gastric banding surgery

Aim:u2002 Hepatic steatosis affects up to 30% of the population. After weight loss, monitoring of the change in hepatic steatosis is not routinely performed. This study aimed to define the closest associates of change in liver fat content in a population of obese females following laparoscopic gastric banding surgery.

In vitro characterisation of intramural neural pathways between the duodenum and the sphincter of Oddi of the brush-tailed possum

The aims of this study were to determine if neural pathways between the duodenum and sphincter of Oddi are intramural, activated by duodenal electrical field stimulation (EFS) in vitro, and contain capsaicin-sensitive primary afferents. The possible involvement of cholinergic (muscarinic and/or nicotinic) and adrenergic receptors in these pathways were also investigated. Duodenal EFS (5-60 Hz, 70 V, 0.5 ms duration, 10 s train) at sites 2 cm oral and 2 cm anal to the sphincter of Oddi-duodenal junction produced frequency-dependent excitatory responses in the sphincter of Oddi, measured by manometry (n = 3). Excitatory responses from duodenal circular muscle were also evident. Tetrodotoxin (1 microM; n = 7) pretreatment abolished both sphincter of Oddi and duodenal responses to duodenal EFS. Crushing the duodenum between the site of stimulation and the sphincter of Oddi-duodenal junction also abolished sphincter of Oddi response. The sphincter of Oddi responses to duodenal EFS at the oral and anal sites were reduced by pretreatment with (i) atropine (100 nM: n = 7) to 19 +/- 6% (P < 0.05) and 22 +/- 8% (P < 0.05) of control respectively. (ii) hexamethonium (100 microM: n = 9) to 10 +/- 2% (P < 0.01) and 6.0 + 2.5% (P < 0.01) of control respectively and (iii) guanethidine (1 microM; n = 6) to 75 +/- 6% (P < 0.05) and 78 +/- 10% (P < 0.05) of control, respectively. Combined pretreatment with phentolamine and propranolol (both 1 microM; n = 7) was without effect, as was capsaicin (1 microM; n = 12) pretreatment. Excitatory intramural pathways between the sphincter of Oddi and the duodenum are primarily cholinergic in nature and contain an adrenergic component. Capsaicin-sensitive primary afferents are not involved.