Effects of the Tibetan herbal formula Padma Lax on visceral nociception and contractility of longitudinal smooth muscle in a rat model.

BACKGROUND: The high prevalence of functional bowel disorders among the general population contrasts with the limited number of pharmacological treatment options for this condition. This has led to an interest for alternative therapeutic approaches. Padma Lax is an herbal laxative on the basis of Tibetan formulas. Our aim is to examine the effect of Padma Lax on visceral nociception in vivo and (B) on contractile activity of longitudinal smooth muscle of the lower gut in vitro and ex vivo. METHODS: (A) Visceral sensory function in response to colorectal distension was assessed by abdominal wall electromyography in male Wistar rats pretreated with Padma Lax. (B) Effects of Padma Lax on contractility of gut smooth muscles were studied both in vitro with superfusion of the agent and ex vivo following oral administration of the preparation. Activities were measured as area under the curve. KEY RESULTS: (A) For visceral sensitivity, no differences were observed between the Padma Lax and the control group. (B) Proximal colon muscle strips of the Padma Lax pretreated group showed significantly lower spontaneous contractility ex vivo than controls. Cholinergic procontractile stimulation was reduced in Padma Lax pretreated group and in colon strips of naive rats when Padma Lax was superfused in vitro (all P < 0.05). CONCLUSION & INFERENCES: Cholinergic mechanisms appear to be important in the modulation of rat proximal colon contractility of orally and directly applied Padma Lax. These findings help elucidate a potential mechanism of action of this herbal remedy which has undergone clinical testing in patients with constipation predominant irritable bowel syndrome.

[Abdominal pain]. / Abdominaler Schmerz.

Abdominal pain can result from a variety of different intra- and extra-abdominal disorders. Given the wide variety of etiological triggers for this pain, the primary task during the first stage of the diagnostic work-up is to determine as soon as possible the underlying cause and the degree of emergency. The aim of this evaluation is to adapt the therapeutic measures which are necessary for a causal treatment to the individual situation. Contrary to somatic causes of abdominal pain, the availability of such a causal therapy for functional bowel disorders is still very limited. Given this dilemma, the therapeutic focus of abdominal pain associated with these functional syndromes has to be placed on symptom-oriented treatment.

Problems of reconstruction during pancreatoduodenectomy.

Pancreatoduodenectomy may be a difficult operation, not only during the resectional part of the procedure, but also during reconstruction. Usually, these problems are due to local conditions of the organs/tissues, such as small diameter of the common bile duct or pancreatic duct, friable soft pancreas, vascular anomalies, etc. Reconstruction may also be problematic because of the hemodynamic instability of the patient during surgery (subsequent to massive hemorrhage), and in those unusual cases, delayed reconstruction may be a life-saving, wise choice.

Mechanism mediating nitric oxide-induced inhibition in human jejunal longitudinal smooth muscle.

BACKGROUND: Enteric neurotransmission is a complex process involving multiple neurotransmitters, including nitric oxide (NO). Our aim was to evaluate the role and mechanism(s) of action of NO in normal human jejunal longitudinal smooth muscle. METHODS: Transmural strips of normal human jejunum obtained from subjects undergoing gastric bypass were studied in organ chambers. Effects of exogenous NO (7 x 10(-6) mol/L to 7 x 10(-5) mol/L) and electrical field stimulation (nonspecific release of endogenous neurotransmitters) on spontaneous contractile activity and on precontracted muscle strips (substance P, 10(-5) mol/L) were evaluated in the presence and absence of the competitive NO synthase inhibitor N(G)-amino-L-arginine (L-NNA, 10(-3) mol/L) and the specific soluble guanylyl cyclase inhibitor 1H-[1,2,4]-oxadiazaolo-[4,3-a]-quinoxalin-1-one (ODQ, 10(-5) mol/L and 10(-4) mol/L). RESULTS: Exogenous NO dose-dependently inhibited spontaneous contractility and relaxed precontracted smooth muscle strips. The effects of NO were markedly attenuated or completely inhibited in the presence of ODQ. Electric field stimulation under nonadrenergic, noncholinergic conditions also inhibited spontaneous contractility and relaxed precontracted smooth muscle strips; both of these effects were attenuated, but not completely inhibited, in the presence of both ODQ and L-NNA. CONCLUSIONS: NO is an endogenous inhibitory neurotransmitter in human jejunal longitudinal smooth muscle, acting at least in part via a mechanism mediated by guanylyl cyclase. Other (non-nitrergic) nonadrenergic, noncholinergic inhibitory neurotransmitters are likely active in this portion of the human gut.

Chronic extrinsic denervation after small bowel transplantation in rat jejunum: Effects and adaptation in nitrergic and non-nitrergic neuromuscular inhibitory mechanisms.

BACKGROUND: Extrinsic denervation of the transplanted small bowel could play a substantial role in motor dysfunction of the transplanted gut. We attempted to determine the effect of chronic extrinsic denervation on intestinal contractility. METHODS: Jejunal longitudinal muscle strips were obtained from rats 1 week and 8 weeks after (1) syngeneic small bowel transplantation, (2) ischemia/reperfusion, or (3) gut transection/reanastomosis. Nonoperated rats (naive controls) and sham-operated rats (sham controls), 1 week after celiotomy/gut manipulation, served as controls. We evaluated the effects of exogenous nitric oxide, increasing doses of cholinergic and adrenergic agonists, and electrical field stimulation (EFS) in the presence or absence of N(G)-monomethyl-l-arginine, methylene blue, tetraethylammonium, or tetrodotoxin. RESULTS: Spontaneous contractile activity (_chi +/- SEM), when compared with the naive controls (11.3 +/- 2.0 g.5 min/mg), was increased in all 4 groups at 1 week (15.9 +/- 10 to 19.4 +/- 2 g.5 min/mg; P < or =.03 each) but not at 8 weeks postoperatively. The inhibition of contractile activity by nitric oxide was increased in small bowel transplantation in naive controls at 8 weeks to 80% +/- 10% versus 50% +/- 7% (P <.02). EFS induced an inhibition of contractile activity that was tetraethylammonium- and tetrodotoxin-sensitive but N(G)-monomethyl-l-arginine- and methylene blue-insensitive; the maximal EFS-induced inhibition was increased at 1 week and 8 weeks but only in the small bowel transplantation groups to 103% +/- 5% and 95% +/- 7%, respectively, versus 72% +/- 8% in naive controls (P

Axillary lymph node dissection in breast cancer--current status and controversies, alternative strategies and future perspectives.

Axillary lymph node dissection (ALND) has traditionally been considered as a standard procedure in the surgical management of patients with breast cancer. The goals of ALND in breast cancer surgery are: (a) to provide accurate prognostic information, (b) to maintain local control of the disease in the axilla and (c) to provide a rational basis for decisions about adjuvant therapy. Although controversial, ALND may also be associated with a small therapeutic benefit. Recently, the question of whether ALND is needed for every patient with invasive breast cancer has been the subject of ongoing debate in the literature. This is mainly due to the widespread use of adjuvant systemic therapy for patients with node-negative breast cancer and to the increasingly frequent detection of small invasive cancers by mammographic screening; the majority of these patients have negative axillae. Sentinel lymph node (SLN) biopsy is a new, promising, minimally invasive procedure, which accurately predicts nodal status with minimal morbidity, and reserves ALND for patients with positive SLN biopsies. However, this method is still investigational. Partial (levels I and II) ALND remains the gold standard in the surgical management of patients with breast cancer.

Prospective evaluation of Roux-en-Y gastric bypass as primary operation for medically complicated obesity.

OBJECTIVE: To determine prospectively the results of Roux-en-Y gastric bypass (RYGB) used as the primary weight-reducing operation in patients with medically complicated ("morbid") obesity. The RYGB procedure combines the advantages of a restrictive physiology (pouch of 10 mL) and a "dumping physiology" for high-energy liquids without requiring an externally reinforced (banded) stoma. PATIENTS AND METHODS: Between April 1987 and December 1998, a total of 191 consecutive patients with morbid obesity (median weight, 138 kg [range, 91-240 kg]; median body mass index, 49 kg/m2 [range, 36-74 kg/m2]), all of whom had directly weight-related morbidity, underwent RYGB and prospective follow-up. RESULTS: Hospital mortality was 0.5% (1/191), and hospital morbidity occurred in 10.5% (20/191). Good long-term weight loss was achieved, and patients adapted well to the required new eating habits. The mean +/- SD weight loss at 1 year after operation (113 patients) was 52 +/- 1 kg or 68% +/- 2% of initial excess body weight. By 3 years postoperatively (74 patients), weight loss was still 66% +/- 2% of excess body weight. Overall, 53 (72%) of 74 patients had achieved and maintained a weight loss of 50% or more of their preoperative excess body weight 3 years after the operation. In addition, only 1 (1%) of 98 patients had persistent postoperative vomiting 1 or more times per week. CONCLUSION: We believe that RYGB is a safe, effective procedure for most patients with morbid obesity and thus may be the current procedure of choice in patients requiring bariatrics++ surgery for morbid obesity.

Bariatric surgery. Surgery for weight control in patients with morbid obesity.

Morbid obesity has become a health crisis in the United States. Medical programs developed at nonoperative attempts to lose (and maintain) an adequate weight loss are largely unsuccessful. Bariatric surgery has been proven to be effective at inducing and maintaining a satisfactory weight loss to decrease weight-related comorbidity. Bariatric operations include procedures that decrease mechanically the volume capacitance of the proximal stomach (vertical banded gastroplasty, laparoscopic gastric banding) or decrease the proximal gastric capacitance and establish a partial selective malabsorption (gastric bypass and its modifications, partial biliopancreatic bypass, and duodenal switch with partial biliopancreatic bypass). These operations should induce a loss of at least 50% (or more) of excess body weight. Not all patients are candidates for these procedures, and the best results are obtained by a multidisciplinary team (including nutritionist, physician, dietitian, psychologist or psychiatrist interested in eating disorders, and surgeon).

Gastroesophageal reflux after intact vertical banded gastroplasty: correction by conversion to Roux-en-Y gastric bypass.

Symptomatic gastroesophageal reflux disease is common in our experience after vertical banded gastroplasty. Our aim was to determine the safety and efficacy of Roux-en-Y gastric bypass in the treatment of symptomatic gastroesophageal reflux disease complicating vertical banded gastroplasty. We evaluated prospectively collected data on 25 patients who underwent revisional bariatric surgery because of severe gastroesophageal reflux disease after vertical banded gastroplasty. Only 4 of 25 patients had gastroesophageal reflux disease symptoms prior to vertical banded gastroplasty. Endoscopic findings in 24 patients included esophagitis (58%), Barrett's esophagus (28%), pouchitis (29%), and gastritis (21%);7 (28%) of 25 patients had evidence of stenosis at the pouch outlet. Mean follow-up (complete in all 25) after Roux-en-Y gastric bypass was 37 +/- 7 months (range 3 to 102 months). There were no deaths. Postoperative complications occurred in six patients: pneumonia in two, wound infection in two, prolonged drainage of the defunctionalized stomach via gastrostomy in one, and fever in one. Median hospitalization was 7 days (range 5 to 43 days). At follow-up (37 +/- 7 months), 24 (96%) of 25 are completely or almost completely symptom free. Body mass index was 33 +/- 2 kg/m(2) before and 28 +/- 2 kg/m(2) after Roux-en-Y gastric bypass (P = 0. 001). Symptoms of gastroesophageal reflux disease are common after vertical banded gastroplasty. Conversion to Roux-en-Y gastric bypass is safe, relieves gastroesophageal reflux disease, and promotes further weight loss. Moreover, maladaptive eating (vomiting, and so forth) induced by vertical banded gastroplasty is relieved.

Nitric oxide pathways in circular muscle of the rat jejunum before and after small bowel transplantation.

Previous studies suggest that nitric oxide synthase is upregulated after small bowel transplantation which may have implications in enteric dysfunction after small bowel transplantation. The aim of this study was to determine the role of nitric oxide in nonadrenergic, noncholinergic inhibitory function after small bowel transplantation in rat jejunal circular muscle. The following four groups of rats (n = >/=8 rats per group) were studied: Neurally intact control animals; 1 week after anesthesia and sham celiotomy, and either 1 week or 8 weeks after isogeneic, orthotopic small bowel transplantation. Full-thickness jejunal circular muscle strips were evaluated under isometric conditions for spontaneous contractile activity, response to electrical field stimulation, and effects of exogenous nitric oxide and nitric oxide antagonists. Spontaneous activity did not differ among groups. Electrical field stimulation inhibited activity similarly in all groups. Exogenous nitric oxide, NG-monomethyl L-arginine monoacetate salt (a nitric oxide synthase inhibitor), and methylene blue (cGMP antagonist) had no effect on spontaneous activity. Neither nitric oxide antagonist altered the inhibitory response to neural excitation by electrical field stimulation in any group. Nitric oxide, a known inhibitory neurotransmitter in other gut smooth muscle, has no apparent role in rat jejunal circular muscle before or after small bowel transplantation.

Small bowel transplantation induces adrenergic hypersensitivity in ileal longitudinal smooth muscle in rats.

Our aim was to determine the effects of small bowel transplantation on contractility of longitudinal muscle in the rat ileum. Full-thickness longitudinal muscle strips from four groups of rats (naive controls, sham-operated controls, and 1 week and 8 weeks after syngeneic orthotopic small bowel transplantation) were studied in vitro. Neither baseline contractility nor response to neural blockade (tetrodotoxin) or adrenergic/cholinergic blockade differed among the groups. Although the dose response to the cholinergic agonist bethanechol and to nitric oxide did not differ among groups, the ED50 (negative log of concentration giving half-maximal effect) for the adrenergic agonist norepinephrine was increased l week and 8 weeks after transplantation, indicating a hypersensitivity response not blocked by tetrodotoxin. Nonadrenergic, noncholinergic inhibitory responses to electrical field stimulation were of greater amplitude and occurred at lesser frequencies (>/=5 Hz) 1 week after small bowel transplantation, but returned to control values 8 weeks postoperatively. These inhibitory responses were blocked by the nitric oxide synthase inhibitor L-NMMA but not by methylene blue, a nonspecific inhibitor of guanylate cyclase. Small bowel transplantation induces a persistent adrenergic denervation hypersensitivity at the muscle and appears to upregulate, at least transiently, other inhibitory mechanisms mediated by neural release of nitric oxide. Small bowel transplantation does not alter muscle response to cholinergic pathways. These alterations in smooth muscle contractility may affect gut function early after clinical small bowel transplantation.

Ten and more years after vertical banded gastroplasty as primary operation for morbid obesity.

Long-term follow-up (>10 years) after vertical banded gastroplasty (VBG) is almost nonexistent. The aim of this study was to determine long-term outcome after VBG in a group of 71 patients studied prospectively. Seventy-one consecutive patients with morbid obesity (54 women and 17 men; mean age 40 years [range 22 to 71 years]) underwent VBG from 1985 to 1989 and were followed prospectively. Follow-up was obtained in 70 (99%) of the 71 patients. Weight (mean +/- standard error of the mean) preoperatively was 138 +/- 3 kg and decreased to 108 +/- 2 kg 10 or more years postoperatively. Body mass index decreased from 49 +/-1 to 39 +/- 1. Only 14 (20%) of 70 patients lost and maintained the loss of at least half of their excess body weight with the VBG anatomy. Vomiting one or more times per week continues to occur in 21% and heartburn in 16%. Fourteen patients have undergone conversion from VBG to Roux-en-Y gastric bypass (11 patients) or other procedures (3 patients) because of a combination of inadequate weight loss in 13 patients, gastroesophageal reflux in five, and frequent vomiting in four. Only 26% of patients after VBG have maintained a weight loss of at least 50% of their excess body weight; 17% underwent bariatric reoperation with good results. Thus VBG is not an effective, durable bariatric operation.

Malabsorptive procedures for severe obesity: comparison of pancreaticobiliary bypass and very very long limb Roux-en-Y gastric bypass.

The aim of this study was to determine the efficacy and safety of two malabsorptive procedures for severe obesity. Prospectively collected data from eight men and three women who underwent partial biliopancreatic bypass (PBB) and 19 men and seven women who underwent very very long limb Roux-en-Y gastric bypass (VVLGB) for superobesity (preoperative weight >225% above ideal body weight) were evaluated. Age (42 +/- 3 years and 40 +/- 2 years), body mass index (64 +/- 4 kg/m(2) and 67 +/- 3 kg/m(2)), and percentage of excess body weight (183% +/- 17% and 203% +/- 12%) were similar (mean +/- standard error of the mean). Median follow-up was 96 months (range 72 to 108 months) and 24 months (range 18 to 60 months) for the PBB and VVLGB groups, respectively. Weight loss expressed as percentage of excess body weight was 68% +/- 4% 2 years and 71% +/- 5% 4 years after PBB, and 53% +/- 7% 2 years and 57% +/- 5% 4 years after VVLGB. Current body mass indexes are 37 +/- 2 kg/m(2) and 42 +/- 2 kg/m(2) in the PBB and VVLGB groups, respectively. Hospital mortality was zero. Morbidity occurred in five patients after VVLGB (wound infection in four, wound seroma in one, and pulmonary embolus in one) and in two patients after PBB (abscess in two, anastomotic leak in one, and gastrointestinal bleeding in one). After PBB, one woman died of refractory liver failure 18 months postoperatively and two other patients developed metabolic bone disease. No such known complications have occurred to date after VVLGB. We conclude that VVLGB is safe and effective for clinically significant obesity, results in sustained weight loss, and improves quality of life.

Role of nitric oxide, vasoactive intestinal polypeptide, and ATP in inhibitory neurotransmission in human jejunum.

BACKGROUND: Inhibitory neurotransmission in the human intestine is poorly understood. This study was undertaken to determine the role of nitric oxide (NO), adenosine triphosphate (ATP), and vasoactive intestinal polypeptide (VIP) in inhibitory neurotransmission in human jejunal circular muscle strips. METHODS: In vitro response of precontracted (10(-5) M substance P) normal human jejunal muscle strips to electric field stimulation (EFS) under adrenergic and cholinergic receptor blockade was evaluated. Selective neural blockade was obtained by the NO synthase inhibitor l-NG-nitroarginine methyl ester (l-NAME, 10(-3) M), VIP receptor antagonist (4-Cl-d-Phe6Leu17-VIP, 10(-7) M), P2 purinergic receptor blocker suramin (3 x 10(14) M), or the calcium-dependent potassium channel blocker apamin (10(-6) M). Force generated in response to EFS was quantitated and analyzed statistically. RESULTS: Exogenous NO and ATP dose-dependently inhibited contractile activity and relaxed muscle strips with a concentration yielding a 50% effect (ED50) of 4.5 +/- 2.9 x 10(-6) M and 3.3 +/- 1.3 x 10(-4) M, respectively. EFS resulted in relaxation of precontracted muscle strips in all groups. When compared with controls, relaxation was decreased but not abolished by l-NAME (-0.12 +/- 0.03 vs -0.33 +/- 0. 05, -0.07 +/- 0.03 vs -0.34 +/- 0.05, and 0.04 +/- 0.03 vs -0.30 +/- 0.04 at 2, 5, and 10 Hz, respectively, P < 0.011). d-NAME (inactive stereoisomer of l-NAME), 4-Cl-d-Phe6Leu17-VIP, suramin, and apamin did not alter EFS-induced relaxation. CONCLUSIONS: Inhibition of NO synthesis by l-NAME reduced the inhibitory response to EFS, whereas blocking ATP and VIP receptors or other effector pathways had no effect. Our findings indicate that although NO plays a predominant role in inhibitory neurotransmission in human jejunal circular muscle, another neurotransmitter(s) appears to be involved as well. These data may impact on understanding mechanisms of disorders of gut dysmotility.

Functional changes in nonadrenergic, noncholinergic inhibitory neurons in ileal circular smooth muscle after small bowel transplantation in rats.

This experiment was designed to determine mechanisms of change in nonadrenergic, noncholinergic (NANC) inhibitory neurons in the ileum after small bowel transplantation (SBT) in the rat and whether nitric oxide (NO) serves as an important NANC inhibitory neurotransmitter in the rat ileum. Eight groups of rats (N > or =8 rats/group) were studied: neurally intact unoperated controls; rats one week after anesthesia and sham celiotomy; and separate groups one and eight weeks after either 40 min of cold ischemia of the jejunoileum, combined jejunal and ileal intestinal transection/reanastomosis, or orthotopic SBT of the entire jejunoileum. Contractile activity was evaluated in full-thickness ileal circular muscle strips under isometric conditions. Spontaneous activity did not differ among groups. In all groups, exogenous NO, NG-monomethyl-L-arginine (L-NMMA, an NO synthase inhibitor), and methylene blue (soluble guanylate cyclase inhibitor) had no effect on spontaneous activity, while 8-bromocyclic guanosine monophosphate (8Br-cGMP) inhibited contractile activity in all groups. Low frequency (2-10 Hz) electrical field stimulation (EFS) inhibited contractile activity only in control and SBT groups; L-NMMA and methylene blue did not alter the response to EFS in any group. These results suggest that each aspect of the SBT procedure, ischemia/reperfusion injury, disruption of enteric neural continuity by intestinal transection, and extrinsic denervation, alter function of enteric ileal inhibitory neurons separately early (one week) after operation. NO, a known inhibitory neurotransmitter in other gut regions, does not affect ileal circular muscle in neurally intact tissue nor mediate functional changes in inhibitory nerve function nor smooth muscle contractility after SBT.

Adrenergic denervation hypersensitivity in ileal circular smooth muscle after small bowel transplantation in rats.

Effects of small bowel transplantation (SBT) on ileal motility are unknown. The aim of the present study was to investigate changes in spontaneous contractile activity and sensitivity to cholinergic and adrenergic agents in the ileal circular muscle after SBT in rats. Orthotopic SBT was performed in syngeneic rats to avoid immune phenomena. Distal ileal circular muscle strips from rats one week (N = 10) and eight weeks (N = 10) after SBT were stretched to optimal length (Lo), and basal spontaneous activity at Lo was measured. Dose-response experiments to the cholinergic agonist bethanechol (Be, 10(-8)-10(-4) M) were performed in the presence of tetrodotoxin (TTX, 10(-6) M) and to the adrenergic agonist norepinephrine (NE, 10(-8)-10(-4) M) with or without TTX. ED50 (negative log of drug-concentration that induced 50% effect) was calculated. We also studied rats with selective jejunoileal ischemia/ reperfusion, intestinal transection/reanastomosis, naive controls, and sham operated controls (N > or = 8/group). Spontaneous basal activity did not differ among groups. Sensitivity to Be was not different in rats after SBT or in other groups compared to control tissue. After SBT, hypersensitivity to NE was shown by a significant increase of ED50 at one and eight weeks after SBT (5.1 +/- 0.3 vs 6.2 +/- 0.4 and 6.2 +/- 0.2, respectively; P < 0.05) regardless of the presence of TTX. No hypersensitivity was observed after ischemia-reperfusion intestinal transection-reanastomosis, or sham operation. It is concluded that ileal hypersensitivity to NE was related to the extrinsic denervation obligated by the transplantation procedure, possibly mediated through an increase in number of receptors on smooth muscle, not on the enteric nerves.

Surgical treatment of obesity: who is an appropriate candidate?

The increasing prevalence and far-reaching medical, social, and economical implications of obesity have made it a national health-care crisis in the United States. About one in every three persons is at least 20% above "ideal" body weight, and approximately 5% have direct weight-related serious health problems (morbid obesity), including hypertension, hyperlipidemia, coronary artery disease, adult-onset diabetes mellitus, degenerative osteoarthropathy, and obstructive sleep apnea. Morbidly obese patients have an estimated 6- to 12-fold increase in mortality. In addition, they have a substantially diminished quality of life, not only physically but also psychosocially due to overt and occult prejudice. Weight reduction must be aggressively pursued in these patients. Medically supervised weight-control programs have been ineffective because patients cannot maintain pronounced long-term weight loss. In contrast, current operative methods have been proved to be effective in helping patients achieve and maintain permanent weight reduction. Several operations have been designed and assessed; with these procedures, weight loss is achieved by inducing malabsorption, maldigestion, early satiety, or a combination of these outcomes. Although these operations have associated side effects and limitations, the expected benefits outweigh the risks. For optimal results, patients must be carefully selected and treated by a multidisciplinary group.