Abstract Neutrophils are increasingly implicated in chronic inflammation and metabolic disorders. Here, we show that visceral adipose tissue (VAT) from individuals with obesity contains more ...neutrophils than in those without obesity and is associated with a distinct bacterial community. Exploring the mechanism, we gavaged microbiome-depleted mice with stool from patients with and without obesity during high-fat or normal diet administration. Only mice receiving high-fat diet and stool from subjects with obesity show enrichment of VAT neutrophils, suggesting donor microbiome and recipient diet determine VAT neutrophilia. A rise in pro-inflammatory CD4+ Th1 cells and a drop in immunoregulatory T cells in VAT only follows if there is a transient spike in neutrophils. Human VAT neutrophils exhibit a distinct gene expression pattern that is found in different human tissues, including tumors. VAT neutrophils and bacteria may be a novel therapeutic target for treating inflammatory-driven complications of obesity, including insulin resistance and colon cancer.
Mast cells express the substance P (SP) neurokinin 1 receptor and the calcitonin gene-related peptide (CGRP) receptor in guinea pig and human small intestine. Enzyme-linked immunoassay showed that ...activation of intramural afferents by antidromic electrical stimulation or by capsaicin released SP and CGRP from human and guinea pig intestinal segments. Electrical stimulation of the afferents evoked slow excitatory postsynaptic potentials (EPSPs) in the enteric nervous system. The slow EPSPs were mediated by tachykinin neurokinin 1 and CGRP receptors. Capsaicin evoked slow EPSP-like responses that were suppressed by antagonists for protease-activated receptor 2. Afferent stimulation evoked slow EPSP-like excitation that was suppressed by mast cell-stabilizing drugs. Histamine and mast cell protease II were released by 1) exposure to SP or CGRP, 2) capsaicin, 3) compound 48/80, 4) elevation of mast cell Ca²⁺ by ionophore A23187, and 5) antidromic electrical stimulation of afferents. The mast cell stabilizers cromolyn and doxantrazole suppressed release of protease II and histamine when evoked by SP, CGRP, capsaicin, A23187, electrical stimulation of afferents, or compound 48/80. Neural blockade by tetrodotoxin prevented mast cell protease II release in response to antidromic electrical stimulation of mesenteric afferents. The results support a hypothesis that afferent innervation of enteric mast cells releases histamine and mast cell protease II, both of which are known to act in a diffuse paracrine manner to influence the behavior of enteric nervous system neurons and to elevate the sensitivity of spinal afferent terminals.
A new type of computer-enhanced telemanipulator device for "robotic" laparoscopic surgery was recently approved. We prospectively evaluated the initial patients undergoing procedures with this new ...device at our institution.
Patient demographics, operative indications, port placement, operative time, robot time, complications, and hospital stay were recorded. Follow-up evaluation was appropriate for the individual procedure.
Initially, 35 cases were managed. There were 22 anti-reflux procedures, 9 Heller myotomies, 1 pyloroplasty, 1 distal pancreatectomy with splenectomy, 1 esophagectomy with intrathoracic anastomosis, and 1 diagnostic laparoscopy. The operative times ranged from 88 to 458 min. The robot use times were between 16 and 185 min. There were no device-related complications.
Computer-enhanced robotic telesurgery is a safe and effective treatment method for a variety of diseases of the proximal gastrointestinal tract. Further study is needed to determine the benefits of this approach as compared with current technology.
In the United States, Roux-en-Y gastric bypass has evolved into the procedure of choice for clinically severe obesity. Stomal stenosis resulting in gastric outlet obstruction is a recognized ...complication. Endoscopic balloon dilation is often used to treat this condition. To evaluate the safety and efficacy of endoscopic management of stomal stenosis we evaluated our treatment methods and outcomes.
The records of all patients undergoing Roux-en-Y gastric bypass from 1 July 2000 to 30 June 2002 were studied. Stenosis was defined as signs and symptoms of obstruction with inability to cannulate the gastrojejunostomy using an 8.5-mm diagnostic endoscope. Charts were reviewed and demographic data, operative course, symptoms, and outcomes were recorded.
A total of 562 patients underwent Roux-en-Y gastric bypass for obesity during the study period. Of these, 38 patients underwent endoscopic balloon dilation for stomal stenosis, for a stenosis rate of 6.8%. The average time from surgery to initial dilation was 7.7 weeks (range 3 to 24). The average number of dilations required was 2.1 (range one to six). The mean initial balloon size was 13 mm and the mean final balloon size was 16 mm. Two patients failed endoscopic dilation and proceeded to surgery, including one patient who developed pneumomediastinum and pneumothorax after dilation. All patients were relieved of their gastric outlet obstruction. The success rate for endoscopic balloon dilation was 95% with a 3% complication rate.
In our experience, the rate of gastrojejunostomy stenosis following Roux-en-Y gastric bypass is 6.8%. Endoscopic balloon dilation is a safe and effective therapy for stomal stenosis with a high success rate. It should be considered an appropriate intervention with a low risk for reoperation.
Robotic resection of pancreatic neuroendocrine tumor Melvin, W S; Needleman, B J; Krause, K R ...
Journal of laparoendoscopic & advanced surgical techniques. Part A,
02/2003, Volume:
13, Issue:
1
Journal Article
Peer reviewed
Computer-assisted surgical devices, or "surgical robots," have recently been approved for general surgical use. The device allows the surgeon remote control of multi-articulated instrument arms with ...a three-dimensional view. Here we report the first known case of pancreatic resection with use of a computer-assisted, or robotic, surgical device. A 46-year old woman presented with back pain and a complex cystic mass in the tail of the pancreas. The daVinci surgical robot was used to remove the lesion en bloc with the tail of the pancreas and spleen. The patient did well and returned to full activity promptly. In summary, robotic technology may enhance advanced laparoscopic procedures. Pancreatic resection is feasible, and future experience will determine the true benefits of this technique.
Obesity has been associated with hypertension, diabetes mellitus, and metabolic syndrome, risk factors for chronic kidney disease. In addition, obesity has been found to have an independent, negative ...effect on renal function and the progression of renal insufficiency.
The serum creatinine (CR) in 813 patients who had undergone obesity surgery from 2003 to 2009 at a large academic medical center and had been followed up for ≥24 months was retrospectively monitored. Renal function, as measured by the CR level, was assessed at baseline and at 6, 12, and ≥24 months of follow-up. The groups were stratified by the baseline CR as follows: normal (CR <1.3 mg/dL), mild impairment (CR 1.3-1.6 mg/dL), and moderate impairment (CR >1.6 mg/dL).
Of the 813 patients, 757 had a CR <1.3 mg/dL at baseline. Of those 757 patients, 97.6% had maintained a CR of <1.3 mg/dL, 1.3% had a CR of 1.3-1.6 mg/dL, 1.1% had a CR of >1.6 mg/dL (n = 757) at 6 months of follow-up. At 1 year of follow-up, 99% had maintained a CR of <1.3 mg/dL and 1% had a CR of >1.3% (n = 509). At 2 years of follow-up, 100% had a CR value of <1.3 mg/dL (n = 388). Of the remaining 56 patients, 71.4% had been classified as having mild impairment (CR 1.3-1.6 mg/dL) and 28.5% as having moderate impairment (CR >1.6 mg/dL) before weight loss surgery. Examination of the CR values at ≥2 years after weight loss surgery demonstrated that 76.7% had a normal CR level, 12.5% had mild impairment, and 10.7% had moderate impairment.
Bariatric surgery does not have a negative effect on renal function as measured by the CR, whether CR at baseline is <1.3 or ≥1.3 mg/dL when monitored for ≥24 months. For those with impaired renal function and a CR ≥1.3 mg/dL, improvement in CR was seen in 76.7% at ≥2 years postoperatively, at a point at which the weight loss velocity, hydration, and nutritional status have stabilized. The weight loss associated with bariatric surgery could potentially have a positive effect on renal function at ≥24 months, such as was found in the present study by a stable or reduced CR level. The etiology for this might be a direct effect of weight loss on impaired renal function or an indirect effect by reducing the rates of co-morbidities, such as diabetes mellitus and hypertension, both risk factors for renal disease. Additional prospective studies, including weight-matched controls, are needed.
Based on findings in rodents, we sought to test the hypothesis that purinergic modulation of synaptic transmission occurs in the human intestine. Time series analysis of intraneuronal free Ca(2+) ...levels in submucosal plexus (SMP) from Roux-en-Y specimens was done using Zeiss LSM laser-scanning confocal fluo-4 AM Ca(2+) imaging. A 3-s fiber tract stimulation (FTS) was used to elicit a synaptic Ca(2+) response. Short-circuit current (I(sc) = chloride secretion) was recorded in mucosa-SMP in flux chambers. A distension reflex or electrical field stimulation was used to study I(sc) responses. Ca(2+) imaging was done in 1,222 neurons responding to high-K(+) depolarization from 61 surgical cases. FTS evoked synaptic Ca(2+) responses in 62% of recorded neurons. FTS caused frequency-dependent Ca(2+) responses (0.1-100 Hz). FTS Ca(2+) responses were inhibited by Omega-conotoxin (70%), hexamethonium (50%), TTX, high Mg(2+)/low Ca(2+) (< or = 100%), or capsaicin (25%). A P2Y(1) receptor (P2Y(1)R) antagonist, MRS-2179 or PLC inhibitor U-73122, blocked FTS responses (75-90%). P2Y(1)R-immunoreactivity occurred in 39% of vasoactive intestinal peptide-positive neurons. The selective adenosine A(3) receptor (AdoA(3)R) agonist 2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (2-Cl-IBMECA) caused concentration- and frequency-dependent inhibition of FTS Ca(2+) responses (IC(50) = 8.5 x 10(-8) M). The AdoA(3)R antagonist MRS-1220 augmented such Ca(2+) responses; 2-Cl-IBMECA competed with MRS-1220. Knockdown of AdoA(1)R with 8-cyclopentyl-3-N-(3-{3-(4-fluorosulphonyl)benzoyl-oxy}-propyl)-1-N-propyl-xanthine did not prevent 2-Cl-IBMECA effects. MRS-1220 caused 31% augmentation of TTX-sensitive distension I(sc) responses. The SMP from Roux-en-Y patients is a suitable model to study synaptic transmission in human enteric nervous system (huENS). The P2Y(1)/Galphaq/PLC/inositol 1,3,5-trisphosphate/Ca(2+) signaling pathway, N-type Ca(2+) channels, nicotinic receptors, and extrinsic nerves contribute to neurotransmission in huENS. Inhibitory AdoA(3)R inhibit nucleotide or cholinergic transmission in the huENS.
Carbon dioxide (CO2) pneumoperitoneum usually is created by a compressed gas source. This exposes the patient to cool dry gas delivered at room temperature (21 degrees C) with 0% relative humidity. ...Various delivery methods are available for humidifying and heating CO2 gas. This study was designed to determine the effects of heating and humidifying gas for the intraabdominal environment.
For this study, 44 patients undergoing laparoscopic Roux-en-Y gastric bypass were randomly assigned to one of four arms in a prospective, randomized, single-blinded fashion: raw CO2 (group 1), heated CO2 (group 2), humidified CO2 (group 3), and heated and humidified CO2 (group 4). A commercially available CO2 heater-humidifier was used. Core temperatures, intraabdominal humidity, perioperative data, and postoperative outcomes were monitored. Peritoneal biopsies were taken in each group at the beginning and end of the case. Biopsies were subjected staining protocols designed to identify structural damage and macrophage activity. Postoperative narcotic use, pain scale scores, recovery room time, and length of hospital stay were recorded. One-way analysis of variance (ANOVA) and the nonparametric Kruskal-Wallis test were used to compare the groups.
Demographics, volume of CO2 used, intraabdominal humidity, bladder temperatures, lens fogging, and operative times were not significantly different between the groups. Core temperatures were stable, and intraabdominal humidity measurements approached 100% for all the patients over the entire procedure. Total narcotic dosage and pain scale scores were not statistically different. Recovery room times and length of hospital stay were similar in all the groups. Only one biopsy in the heated-humidified group showed an increase in macrophage activity.
The intraabdominal environment in terms of temperature and humidity was similar in all the groups. There was no significant difference in the intraoperative body temperatures or the postoperative variable measured. No histologic changes were identified. Heating or humidifying of CO2 is not justified for patients undergoing laparoscopic bariatric surgery.
Microtubules are hollow cylinders composed of tubulin heterodimers that stack into linear protofilaments that interact laterally to form the microtubule wall. Synchrotron x-ray diffraction of ...microtubules under increasing osmotic stress shows they transition to rectangular bundles with noncircular buckled cross sections, followed by hexagonally packed bundles. This new technique probes the strength of interprotofilamen bonds, yielding insight into the mechanism by which associated proteins and the chemotherapy drug taxol stabilize microtubules.
Background and Aims Treatments with morphine or opioid agonists cause constipation. Lubiprostone is approved for treatment of adult idiopathic constipation and constipation-predominant IBS in adult ...women. We tested whether lubiprostone can reverse morphine-suppression of mucosal secretion in human intestine and explored the mechanism of action. Methods Fresh segments of jejunum discarded during Roux-En-Y gastric bypass surgeries were used. Changes in short-circuit current (ΔIsc) were recorded in Ussing flux chambers as a marker for electrogenic chloride secretion during pharmacological interactions between morphine, prostaglandin receptor antagonists, chloride channel blockers and lubiprostone. Results Morphine suppressed basal Isc. Lubiprostone reversed morphine suppression of basal Isc. Lubiprostone, applied to the mucosa in concentrations ranging from 3 nM to 30 μM, evoked increases in Isc in concentration-dependent manner when applied to the mucosal side of muscle-stripped preparations. Blockade of enteric nerves did not change stimulation of Isc by lubiprostone. Removal of chloride or application of bumetanide or NPPB suppressed or abolished responses to lubiprostone. Antagonists acting at CFTR channels and prostaglandin EP₄ receptors, but not at E₁, EP₁₋₃ receptors, partially suppressed stimulation of Isc by lubiprostone. Conclusions Antisecretory action of morphine results from suppression of excitability of secretomotor neurons in the enteric nervous system. Lubiprostone, which does not affect enteric neurons directly, bypasses the action of morphine by directly opening mucosal chloride channels.
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