Selection of electrical algorithms to treat obesity with intermittent vagal block using an implantable medical device.

BACKGROUND: A laparoscopically implantable electrical device that intermittently blocks both vagi near the esophagogastric junction led to significant excess weight loss (EWL) in an initial clinical trial in obese patients. The study objective was to optimize therapy algorithms and determine the EWL achieved with a second-generation device at university hospitals in Australia, Norway, and Switzerland. METHODS: Data acquired during the initial clinical trial were analyzed and subsequently used to select alternative electrical algorithms. In the second trial, vagal blocking using one selected therapy algorithm was initiated 2 weeks after implanting the second-generation device. The patients were followed up for 6 months to assess the EWL and safety, including adverse events. RESULTS: In the initial clinical trial, vagal blocking algorithm durations of 90-150 s were associated with greater EWL compared with either shorter or longer algorithm durations (P<.01). The second trial enrolled 27 patients (mean body mass index 39.3+/-.8 kg/m2) to evaluate a 120-s blocking algorithm. At 6 months, greater EWL was achieved (22.7%+/-3.1%, n=24) compared with the initial study and first-generation device (14.2%+/-2.2%, n=29, P=.03). In both trials, an association was found between the number of 90-150-s algorithms delivered daily and greater EWL (P=.03). No deaths, unanticipated device-related adverse events, or medically serious adverse events were associated with the device. CONCLUSION: This second-generation vagal blocking device, using a therapy algorithm of 120-s duration, resulted in a clinically acceptable safety profile and significantly greater EWL compared with the first-generation device delivering a wider range of therapy algorithm durations.

The effect of morphine on mast cell-mediated mucosal permeability.

BACKGROUND: The late phase of post-traumatic multisystem organ failure is associated with sepsis from organisms that normally reside within the gut's lumen. Morphine, a commonly employed analgesic in injured patients, is associated with intestinal stasis, bacterial overgrowth, and translocation when administered to rats. N-formyl-methionyl-leucyl-phenylalanine (FMLP), a toxic product of gram-negative organisms, provokes an increase in mucosal permeability when infused into the ileal lumen of this species. The current study was designed to examine the effects of morphine on FMLP perturbation of the mucosal barrier of the ileum of rats and mice to an impermeant macromolecule, dextran 4400. The potential role of mucosal mast cells in the response to either agent alone or in combination was examined. METHODS: Intact and isolated segments of distal ileum of naïve and sensitized (Trichinella spiralis and egg albumin) Sprague-Dawley rats were exposed to FMLP with or without morphine or doxantrazole, a mast cell-stabilizing agent. Isolated segments of distal ileum of mast cell-deficient mice also were studied. RESULTS: Mucosal exposure of distal ileal mucosa (intact and isolated, and naive and sensitized) to FMLP was associated with an increase in permeability to dextran 4400, which was completely ablated by morphine and doxantrazole. Sensitization was associated with a prolongation of the FMLP response. Ilea of mast cell-deficient mice (but not their wild type litter mates) were unresponsive to FMLP. CONCLUSIONS: Morphine antagonizes the provocative effect of FMLP on the mucosal barrier to dextran 4400 of the ilea of rats and mice. Intestinal mucosal mast cells play a central role in the process.

Body weight, insulin resistance, and serum adipokine levels 2 years after 2 types of bariatric surgery.

OBJECTIVE: Bariatric surgery reverses obesity-related comorbidities, including type 2 diabetes mellitus. Several studies have already described differences in anthropometrics and body composition in patients undergoing Roux-en-Y gastric bypass compared with laparoscopic adjustable gastric banding, but the role of adipokines in the outcomes after the different types of surgery is not known. Differences in weight loss and reversal of insulin resistance exist between the 2 groups and correlate with changes in adipokines. METHODS: Fifteen severely obese women (mean body mass index [BMI]: 46.7 kg/m(2)) underwent 2 types of laparoscopic weight loss surgery (Roux-en-Y gastric bypass=10, adjustable gastric banding=5). Weight, waist and hip circumference, body composition, plasma metabolic markers, and lipids were measured at set intervals during a 24-month period after surgery. RESULTS: At 24 months, patients who underwent Roux-en-Y were overweight (BMI 29.7 kg/m(2)), whereas patients who underwent gastric banding remained obese (BMI 36.3 kg/m(2)). Patients who underwent Roux-en-Y lost significantly more fat mass than patients who underwent gastric banding (mean difference 16.8 kg, P<.05). Likewise, leptin levels were lower in the patients who underwent Roux-en-Y (P=.003), and levels correlated with weight loss, loss of fat mass, insulin levels, and Homeostasis Model of Assessment 2. Adiponectin correlated with insulin levels and Homeostasis Model of Assessment 2 (r=-0.653, P=.04 and r=-0.674, P=.032, respectively) in the patients who underwent Roux-en-Y at 24 months. CONCLUSION: After 2 years, weight loss and normalization of metabolic parameters were less pronounced in patients who underwent gastric banding compared with patients who underwent Roux-en-Y gastric bypass. Our findings require confirmation in a prospective randomized trial.

Dramatic reversal of derangements in muscle metabolism and left ventricular function after bariatric surgery.

OBJECTIVE: The study objective was to define muscle metabolic and cardiovascular changes after surgical intervention in clinically severe obese patients. METHODS: Obesity is a state of metabolic dysregulation that can lead to maladaptive changes in heart and skeletal muscle, including insulin resistance and heart failure. In a prospective longitudinal study, 43 consecutive patients underwent metabolic profiling, skeletal muscle biopsies, and resting echocardiograms at baseline and 3 and 9 months after bariatric surgery. RESULTS: Body mass index decreased (mean changes, 95% confidence interval [CI]): 7.7 kg/m(2) (95% CI, 6.70-8.89) at 3 months and 5.6 kg/m(2) (95% CI, 4.45-6.80; P<.0001) at 9 months after surgery, with restoration of insulin sensitivity and decreases in plasma leptin at the same time points. Concurrent with these changes were dramatic decreases in skeletal muscle transcript levels of stearoyl coenzyme-A desaturase and pyruvate dehydrogenase kinase-4 at 3 and 9 months (P<.0001, for both) and a significant decrease in peroxisome proliferation activated receptor-alpha-regulated genes at 9 months. Left ventricular relaxation impairment, assessed by tissue Doppler imaging, normalized 9 months after surgery. CONCLUSION: Weight loss results in the reversal of systemic and muscle metabolic derangements and is accompanied by a normalization of left ventricular diastolic function.

Alteraçöes da motricidade do esfíncter de Oddi secundárias à administraçäo de algumas drogas / Changes in the motility of the Oddi's sphincter following administration of some drug's

A eletromiografia do esfíncter de Oddi foi realizada em 32 opossums após a administraçäo de álcool etílico, analgésicos, drogas autonômicas e nifedipina. Seis ou sete pares de eletrodos foram implantados no esfíncter de Oddi e intestino delgado e um cateter foi inserido no duodeno ou veia jugular, para a administraçäo de drogas. A instilaçäo intraduodenal de álcool causou um aumento significativo na freqüência de potenciais de açäo (7,4 potenciais/min) por 15 a 20 minutos no esfíncter de Oddi, em todos experimentos. A morfina, a meperidina e a pentazocina causaram um aumento na duraçäo do complexo mioelétrico migratório de 85,4 minutos a 167,7, 143,4 e 129,1 minutos, respectivamente. Períodos de atividade mioelétrica intensa de 1-2 minutos foram observados após a administraçäo da morfina em oito experimentos, da meperidina em seis e da pentazocina em 3. O betanecol aumentou e a atropina aboliu os potenciais de açäo no esfíncter de Oddi e duodeno. A fenilefrina aumentou a motricidade do esfíncter de Oddi, mas diminuiu a freqüência de potenciais de açäo no duodeno. A clonidina, a dobutamina e a terbutalina diminuíram a freqüência de potenciais de açäo no esfíncter de Oddi e duodeno. A infusäo de nifedipina, um bloqueador do canal de cálcio, reduziu a freqüência de potenciais de açäo no esfíncter de Oddi e intestino delgado. Esta reduçäo era dependente da dose infundida. A infusäo de nifedipina a doses elevadas aboliu o complexo mioelétrico migratório no trato gastrintestinal

Physiopathological evaluation of the sphincter of Oddi

Recentemente, a colangiografia com radioisótopos, a eletromiografia e a manometria endoscópica com o emprego de um cateter de infusäo ou com um microtransdutor têm sido utilizados na avaliaçäo do esfíncter de Oddi. A eletromiografia do esfíncter de Oddi associada à cineradiografia e fluxometria confirmaram que o esfíncter de Oddi do opossum apresenta contraçöes peristáticas e funciona como um aparelho ejaculador. Apesar do mecanismo de fluxo biliar através do esfíncter de Oddi no homem ainda ser controvertido, vários estudos de manometria endoscópica sugerem que o esfíncter de Oddi do homem pode também funcionar como uma bomba. A elevaçäo da pressäo basal do esfíncter de Oddi é a alteraçäo mais comum observada durante a manometria endoscópica de pacientes com estenose papilar e alteraçöes funcionais do esfíncter de Oddi. O valor do teste da morfina-prostigmina no diagnóstico da estenose papilar é controvertido

Efeito de estímulos fisiológicos sobre a motricidade do esfíncter de Oddi / Effect of physiological stimuli on the Oddi's sphincter motility

A atividade mioelétrica do esfíncter de Oddi foi avaliada tanto nos estados de jejum, como prandial e após a administraçäo de hormônios gastrointestinais que podem desempenhar uma importante funçäo no controle da motricidade do esfíncter de Oddi. A eletromiografia do esfíncter de Oddi e do trato gastrointestinal foi realizada em 21 opossums em jejum e após a administraçäo de 20 Cal/kg de lipídios, proteínas, carboidratos ou de uma mistura isocalórica desses três alimentos. O efeito de hormônios gastrointestinais (colecistoquinina, gastrina, glucagon e secretina) também foi estudado. O segmento proximal do esfíncter de Oddi gerou potenciais de açäo espontâneos que se propagaram para o segmento distal do esfíncter. O esfíncter de Oddi apresenta uma variaçäo na freqüência dos potenciais de açäo durante o jejum que se correlaciona com a atividade mioelétrica do trato gastrointestinal, denominada complexo mioelétrico migratório. Após a administraçäo de alimentos, o complexo mioelétrico migratório foi abolido e substituído por um outro de atividade mioelétrica prandial, cuja duraçäo e freqüência dos potenciais de açäo dependiam do tipo de alimento. A colecistoquinina e a pentagastrina aumentaram e o glucagon e a secretina diminuiram a freqüência dos potenciais de açäo no esfíncter de Oddi. Conclui-se que o esfíncter de Oddi pode desempenhar a funçäo importante de propelir e coordenar o tempo e o volume de drenagem para o duodeno

Drenagem biliar pré-operatória / Preoperative biliary drainage

Um grupo de 36 pacientes com icterícia extra-hepática secundária à obstruçäo da via biliar principal por carcinoma do pâncreas foi submetido ao tratamento cirúrgico com ou sem drenagem biliar pré-operatória ou a um tratamento paliativo com colocaçäo de prótese no colédoco. Näo houve diferença na incidência de morbidade e mortalidade entre os grupos submetidos ao tratamento cirúrgico com ou sem drenagem biliar pré-operatória. Um estudo experimental foi realizado em 60 ratos para determinar se existe diferença na taxa de mortalidade entre animais submetidos à drenagem biliar interna e externa. A mortalidade pós-operatória foi de 83,3% nos animais submetidos a somente ligadura do colédoco, 25% nos animais com ligadura do colédoco e drenagem biliar interna, 63% nos animais com ligadura do colédoco e drenagem biliar externa e 16,5% nos controles. Conclui-se que a drenagem biliar interna é superior à drenagem biliar externa na reduçäo da mortalidade pós-operatória que ocorre na icterícia obstrutiva

Correlation between biliopancreatic pressure and electromyography of the sphincter of oddi after various stimuli

Registros simultâneos das atividades eletromiográficas do esfíncter de Oddi e duodeno e das pressöes biliar e pancreática foram obtidos de 16 opossums. Os estudos foram realizados com os animais em jejum, após a ingestäo de alimentos e a administraçäo endovenosa de colecistoquinina, pentagastrina, secretina e glucagon. A freqüência de potenciais de açäo no esfíncter de Oddi durante o estado de jejum era irregular e variava de acordo com as fases do complexo mioelétrico migratório no duodeno. Após a ingestäo de alimentos, o complexo miolétrico foi abolido e substituído pelo padräo mioelétrico alimentar. Colecistoquinina e pentagastrina aumentaram e glucagon e secretina diminuíram a freqüência de potenciais de açäo no esfíncter de Oddi e duodeno. As pressöes pancreáticas e biliares médias foram 15 e 13 mmHg respectivamente. A pressäo basal permaneceu constante durante o estado de jejum, após a ingestäo de alimentos e durante a administraçäo de colecistoquinina, pentagastrina, glucagon e secretina. O esfíncter de Oddi provavelmente tem uma funçäo importante de coordenar o tempo e a quantidade de bile e suco pancreático que säo secretados no duodeno