Mesh vs. non-mesh repair of type I hiatal hernias: a propensity-score matching analysis of 6533 patients from the Herniamed registry.

INTRODUCTION: Surgical treatment of type I hiatal sliding hernias aims to control the gastroesophageal reflux symptoms and prevention of hernia recurrence. Usually, a cruroplasty is performed to narrow the hiatal orifice. Here, it remains controversial if a mesh reinforcement of the cruroplasty should be performed, since benefits as well as mesh-associated complications have been described. METHODS: We performed a propensity-score matching analysis with data derived from the Herniamed registry comparing patients undergoing laparoscopic type I hiatal hernia repair with and without synthetic mesh. We analyzed perioperative, intraoperative, and postoperative data including data derived from the 1-year follow-up in the registry. RESULTS: 6.533 patients with an axial, type I hiatal hernia and gastroesophageal reflux are included in this analysis. Mesh augmentation of the hiatoplasty was performed in n = 1.252/6.533 (19.2%) of patients. The defect size in the subgroup of patients with mesh augmentation was with mean 16.3 cm2 [14.5; 18.2] significantly larger as in the subgroups without mesh augmentation with 10.8 cm2 [8.7; 12.9]; (p < 0.001). In patients with mesh hiatoplasty n = 479 (38.3%) Nissen and n = 773 (61.7%) Toupet fundoplications are performed. 1.207 matched pairs could be analyzed. The mean defect size after matching was with 15.9 cm2 comparable in both groups. A significant association was seen regarding recurrence (4.72% mesh vs. 7.29% non-mesh hiatoplasty, p = 0.012). The same relation can be seen for pain on exertion (8.78% vs 12.10%; p = 0.014) and pain requiring treatment (6.13% vs 9.11%; p = 0.010). All other outcome parameter showed no significant correlation. CONCLUSIONS: Our data demonstrate that mesh-reinforced laparoscopic type I hiatal hernia repair in larger defects is associated with significantly lower rates for recurrence, pain on exertion and pain requiring treatment.

Gender differences in epigastric hernia repair: a propensity score matching analysis of 15,925 patients from the Herniamed registry.

INTRODUCTION: In recent surgical literature, gender-specific differences in the outcome of hernia surgery has been analyzed. We already know that female patients are at higher risk to develop chronic postoperative pain after inguinal, incisional, and umbilical hernia surgery. In this study, we evaluated the impact of gender on the outcome after epigastric hernia surgery. METHODS: A covariable-adjusted matched-paired analysis with data derived from the Herniamed registry was performed. In total of 15,925 patients with 1-year follow-up data were included in the study. Propensity score matching was performed for the 7786 female (48.9%) and 8139 male (51.1%) patients, creating 6350 pairs (81.6%). RESULTS: Matched-paired analysis revealed a significant disadvantage for female patients for pain on exertion (12.1% vs. 7.6%; p < 0.001) compared to male patients. The same effect was demonstrated for pain at rest (6.2% in female patients vs. 4.1% in male patients; p < 0.001) and pain requiring treatment (4.6% in female patients vs. 3.1% in male patients; p < 0.001). All other outcome parameters showed no significant differences between female and male patients. CONCLUSIONS: Female patients are at a higher risk for chronic pain after elective epigastric hernia repairs compared to the male patient population. These results complete findings of previous studies showing the same effect in inguinal, umbilical, and incisional hernia repair.

Potential influencing factors on the outcome in incisional hernia repair: a registry-based multivariable analysis of 22,895 patients.

INTRODUCTION: Due to the paucity of randomized controlled trials, meta-analyses of incisional hernia repair can hardly give any insights into the influence factors on the various outcome criteria. Therefore, a multivariable analysis of data from the Herniamed Registry was undertaken with the aim to define potential influencing factors for the outcome. METHODS: Multivariable analysis of the data available for 22,895 patients with primary elective incisional hernia repair was performed to assess the confirmatory predefined potential influence factors and their association with the perioperative and 1-year follow-up outcomes. A model validation procedure was implemented using a bootstrap algorithm in order to account for the robustness of results. RESULTS: Higher European Hernia Society (EHS) width classification, open procedure, female gender, and preoperative pain have a highly significant association with an unfavorable outcome in incisional hernia repair. Larger defect width and open operation have a highly significantly unfavorable relation to the postoperative surgical complications, general complications, and the complication-related reoperations, while female gender and preoperative pain have a highly significantly unfavorable association with the rates of pain at rest, pain on exertion, and chronic pain requiring treatment at 1-year follow-up. The recurrence rate is significantly unfavorably influenced by higher EHS width classification, higher BMI, and lateral EHS classification. CONCLUSION: Higher EHS width classification, open procedure, female gender, higher BMI, and lateral EHS classification, as well as preoperative pain are the most important unfavorable influencing factors associated with a worse outcome in incisional hernia repair.

Analysis of 4,015 recurrent incisional hernia repairs from the Herniamed registry: risk factors and outcomes.

INTRODUCTION: The proportion of recurrences in the total collective of all incisional hernias has been reported to be around 25%. In the European Hernia Society (EHS) classification, recurrent incisional hernias are assigned to a unique prognostic group and considered as complex abdominal wall hernias. Surgical repairs are characterized by dense adhesions, flawed anatomical planes caused by previous dissection or mesh use, and device-related complications. To date, only relatively small case series have been published focusing on outcomes following recurrent incisional hernia repair. This cohort study now analyzes the outcome of recurrent incisional hernia repair assessing potential risk factors based on data from the Herniamed registry. Special attention is paid to the technique used during the primary incisional hernia repair, since laparoscopic IPOM was recently deemed to cause more complications during subsequent repairs. METHODS: In the multicenter Internet-based Herniamed registry, patients with recurrent incisional hernia repair between September 2009 and January 2018 were enrolled. In a confirmatory multivariable analysis, factors potentially associated with the outcome parameters (intraoperative, postoperative and general complications, complication-related reoperations, re-recurrences, pain at rest and on exertion, and chronic pain requiring treatment at one-year follow-up) were evaluated. RESULTS: In total, 4015 patients from 712 participating hospitals were included. Postoperative complications and complication-related reoperations were significantly associated with larger recurrent hernia defect size, open recurrent incisional hernia repair and the use of larger meshes. General complications were more frequent in female sex patients and when larger meshes were used. Higher re-recurrence rate was observed with lateral defect localization, present risk factors, and time interval ≤ 1 year between primary and recurrent incisional hernia repair. Pain rates at 1-year follow-up were unfavorably related with pre-existing preoperative pain, female sex, lateral defect localization, larger mesh, presence of risk factors, and postoperative complications. As regards the primary incisional hernia repair technique, laparoscopic IPOM was found to show no effect versus open mesh techniques on the subsequent recurrence repair, despite a trend toward higher rates of complication-related reoperations. CONCLUSION: The outcomes of recurrent incisional hernia repair were significantly associated with potential influencing factors, which are very similar to the factors seen in primary incisional hernia repair. The impact of the primary incisional hernia repair technique, namely laparoscopic IPOM versus open mesh techniques, on the outcome of recurrent incisional hernia repair seems less pronounced than anticipated.

Female sex as independent risk factor for chronic pain following elective incisional hernia repair: registry-based, propensity score-matched comparison.

INTRODUCTION: To date, little attention has been paid by surgical scientific studies to sex as a potential influence factor on the outcome. Therefore, there is a sex bias in the surgical literature. With an incidence of more than 20% after 3 years, incisional hernias are a common complication following abdominal surgical procedures. The proportion of women affected is around 50%. There are very few references in the literature to the influence of sex on the outcome of elective incisional hernia repair. MATERIALS AND METHODS: In all, 22,895 patients with elective incisional hernia repair from the Herniamed Registry were included in the study. The patients had undergone elective incisional hernia repair in a laparoscopic IPOM, open sublay, open IPOM, open onlay or suture technique. 1-year follow-up was available for all patients. Propensity score matching was performed for the 11,480 female (50.1%) and 11,415 male (49.9%) patients, creating 8138 pairs (82.0%) within fixed surgical procedures. RESULTS: For pain on exertion (11.7% vs 18.3%; p < 0.001), pain at rest (7.53% vs 11.1%; p < 0.001), and pain requiring treatment (5.4% vs 9.1%; p < 0.001) highly significant disadvantages were identified for the female sex when comparing the different results within the matched pairs. That was also confirmed on comparing sex within the individual surgical procedures. No sex-specific differences were identified for the postoperative complications, complication-related reoperations or recurrences. Less favorable intraoperative complication results in the female sex were observed only for the onlay technique. CONCLUSIONS: Female sex is an independent risk factor for chronic pain after elective incisional hernia repair.

Update of Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias (International Endohernia Society (IEHS)): Part B.

In 2014 the International Endohernia Society (IEHS) published the first international "Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias". Guidelines reflect the currently best available evidence in diagnostics and therapy and give recommendations to help surgeons to standardize their techniques and to improve their results. However, science is a dynamic field which is continuously developing. Therefore, guidelines require regular updates to keep pace with the evolving literature. METHODS: For the development of the original guidelines all relevant literature published up to year 2012 was analyzed using the ranking of the Oxford Centre for Evidence-Based-Medicine. For the present update all of the previous authors were asked to evaluate the literature published during the recent years from 2012 to 2017 and revise their statements and recommendations given in the initial guidelines accordingly. In two Consensus Conferences (October 2017 Beijing, March 2018 Cologne) the updates were presented, discussed, and confirmed. To avoid redundancy, only new statements or recommendations are included in this paper. Therefore, for full understanding both of the guidelines, the original and the current, must be read. In addition, the new developments in repair of abdominal wall hernias like surgical techniques within the abdominal wall, release operations (transversus muscle release, component separation), Botox application, and robot-assisted repair methods were included. RESULTS: Due to an increase of the number of patients and further development of surgical techniques, repair of primary and secondary abdominal wall hernias attracts increasing interests of many surgeons. Whereas up to three decades ago hernia-related publications did not exceed 20 per year, currently this number is about 10-fold higher. Recent years are characterized by the advent of new techniques-minimal invasive techniques using robotics and laparoscopy, totally extraperitoneal repairs, novel myofascial release techniques for optimal closure of large defects, and Botox for relaxing the abdominal wall. Furthermore, a concomitant rectus diastasis was recognized as a significant risk factor for recurrence. Despite still insufficient evidence with respect to these new techniques it seemed to us necessary to include them in the update to stimulate surgeons to do research in these fields. CONCLUSION: Guidelines are recommendations based on best available evidence intended to help the surgeon to improve the quality of his daily work. However, science is a continuously evolving process, and as such guidelines should be updated about every 3 years. For a comprehensive reference, however, it is suggested to read both the initially guidelines published in 2014 together with the update. Moreover, the presented update includes also techniques which were not known 3 years before.

Correction to: Update of Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias (International Endohernia Society (IEHS))-Part A.

This article was updated to include the middle initial of author L. N. Jorgensen's name.

Update of Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias (International Endohernia Society (IEHS))-Part A.

In 2014, the International Endohernia Society (IEHS) published the first international "Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias." Guidelines reflect the currently best available evidence in diagnostics and therapy and give recommendations to help surgeons to standardize their techniques and to improve their results. However, science is a dynamic field which is continuously developing. Therefore, guidelines require regular updates to keep pace with the evolving literature. METHODS: For the development of the original guidelines, all relevant literature published up to year 2012 was analyzed using the ranking of the Oxford Centre for Evidence-Based Medicine. For the present update, all of the previous authors were asked to evaluate the literature published during the recent years from 2012 to 2017 and revise their statements and recommendations given in the initial guidelines accordingly. In two Consensus Conferences (October 2017 Beijing, March 2018 Cologne), the updates were presented, discussed, and confirmed. To avoid redundancy, only new statements or recommendations are included in this paper. Therefore, for full understanding both of the guidelines, the original and the current, must be read. In addition, the new developments in repair of abdominal wall hernias like surgical techniques within the abdominal wall, release operations (transversus muscle release, component separation), Botox application, and robot-assisted repair methods were included. RESULTS: Due to an increase of the number of patients and further development of surgical techniques, repair of primary and secondary abdominal wall hernias attracts increasing interests of many surgeons. Whereas up to three decades ago hernia-related publications did not exceed 20 per year, currently this number is about 10-fold higher. Recent years are characterized by the advent of new techniques-minimal invasive techniques using robotics and laparoscopy, totally extraperitoneal repairs, novel myofascial release techniques for optimal closure of large defects, and Botox for relaxing the abdominal wall. Furthermore, a concomitant rectus diastasis was recognized as a significant risk factor for recurrence. Despite insufficient evidence with respect to these new techniques, it seemed to us necessary to include them in the update to stimulate surgeons to do research in these fields. CONCLUSION: Guidelines are recommendations based on best available evidence intended to help the surgeon to improve the quality of his daily work. However, science is a continuously evolving process, and as such guidelines should be updated about every 3 years. For a comprehensive reference, however, it is suggested to read both the initial guidelines published in 2014 together with the update. Moreover, the presented update includes also techniques which were not known 3 years before.

Characteristics of the K+-competitive H+,K+-ATPase inhibitor AZD0865 in isolated rat gastric glands.

The gastric H+,K+-ATPase of the parietal cell is responsible for acid secretion in the stomach and is the main target in the pharmacological treatment of acid-related diseases. Omeprazole and other benzimidazole drugs, although having delayed efficacy if taken orally, have high success rates in the treatment of peptic ulcer disease. Potassium competitive acid blockers (P-CAB) compete with K+ for binding to the H+,K+-ATPase and thereby they inhibit acid secretion. In this study, the in vitro properties of AZD0865, a reversible H+,K+-ATPase inhibitor of gastric acid secretion, are described. We used a digital-imaging system and the pH sensitive dye BCECF to observe proton efflux from hand-dissected rat gastric glands. Glands were stimulated with histamine (100 microM) and exposed to a bicarbonate- and Na+-free perfusate to induce an acid load. H+,K+-ATPase inhibition was determined by calculating pHi recovery (dpH/dT) in the presence of omeprazole (10-200 microM) or AZD0865 (0.01-100 microM). The efficacies of both drugs were compared. Our data show that acid secretion is inhibited by both the proton pump inhibitor omeprazole and the P-CAB AZD0865. Complete inhibition of acid secretion by AZD0865 had a rapid onset of activation, was reversible, and occurred at a 100-fold lower dose than omeprazole (1 microM AZD0865 vs. 100 microM omeprazole). This study demonstrates that AZD0865 is a potent, fast-acting inhibitor of gastric acid secretion, effective at lower concentrations than drugs of the benzimidazole class. Therefore, these data strongly suggest that AZD0865 has great potential as a fast-acting, low-dose inhibitor of acid secretion.

Role of calcium and other trace elements in the gastrointestinal physiology.

Calcium is an essential ion in both marine and terrestrial organisms, where it plays a crucial role in processes ranging from the formation and maintenance of the skeleton to the regulation of neuronal function. The Ca(2+) balance is maintained by three organ systems, including the gastrointestinal tract, bone and kidney. Since first being cloned in 1993 the Ca(2+)-sensing receptor has been expressed along the entire gastrointestinal tract, until now the exact function is only partly elucidated. As of this date it still remains to be determined if the Ca(2+)-sensing receptor is involved in calcium handling by the gastrointestinal tract. However, there are few studies showing physiological effects of the Ca(2+)-sensing receptor on gastric acid secretion and fluid transport in the colon. In addition, polyamines and amino acids have been shown to activate the Ca(2+)-sensing receptor and also act as allosteric modifiers to signal nutrient availability to intestinal epithelial cells. Activation of the colonic Ca(2+)-sensing receptor can abrogate cyclic nucleotide-mediated fluid secretion suggesting a role of the receptor in modifying secretory diarrheas like cholera. For many cell types changes in extracellular Ca(2+) concentration can switch the cellular behavior from proliferation to terminal differentiation or quiescence. As cancer remains predominantly a disease of disordered balance between proliferation, termination and apoptosis, disruption in the function of the Ca(2+)-sensing receptor may contribute to the progression of neoplastic disease. Loss of the growth suppressing effects of elevated extracellular Ca(2+) have been demonstrated in colon carcinoma, and have been correlated with changes in the level of CaSR expression.

The stomach divalent ion-sensing receptor scar is a modulator of gastric acid secretion.

Divalent cation receptors have recently been identified in a wide variety of tissues and organs, yet their exact function remains controversial. We have previously identified a member of this receptor family in the stomach and have demonstrated that it is localized to the parietal cell, the acid secretory cell of the gastric gland. The activation of acid secretion has been classically defined as being regulated by two pathways: a neuronal pathway (mediated by acetylcholine) and an endocrine pathway (mediated by gastrin and histamine). Here, we identified a novel pathway modulating gastric acid secretion through the stomach calcium-sensing receptor (SCAR) located on the basolateral membrane of gastric parietal cells. Activation of SCAR in the intact rat gastric gland by divalent cations (Ca(2+) or Mg(2+)) or by the potent stimulator gadolinium (Gd(3+)) led to an increase in the rate of acid secretion through the apical H+,K+ -ATPase. Gd(3+) was able to activate acid secretion through the omeprazole-sensitive H+,K+ -ATPase even in the absence of the classical stimulator histamine. In contrast, inhibition of SCAR by reduction of extracellular cations abolished the stimulatory effect of histamine on gastric acid secretion, providing evidence for the regulation of the proton secretory transport protein by the receptor. These studies present the first example of a member of the divalent cation receptors modulating a plasma membrane transport protein and may lead to new insights into the regulation of gastric acid secretion.

Anaphylactic reactions to aprotinin reexposure in cardiac surgery: relation to antiaprotinin immunoglobulin G and E antibodies.

BACKGROUND: Aprotinin, a serine proteinase inhibitor, reduces bleeding during cardiac surgery. As aprotinin is derived from bovine lung, it has antigenic properties. This investigation examined the incidence of anaphylactic reactions in patients reexposed to aprotinin and the relation to preformed antiaprotinin immunoglobulin (Ig)G and IgE antibodies. METHODS: This prospective observational study conducted at five centers in Germany evaluated patients undergoing repeat cardiac surgery reexposed to aprotinin between 1995 and 1996. Antiaprotinin IgG and IgE antibody measurements, using a noncommercial enzyme-linked immunosorbent assay and an immunofluorescence assay, respectively, were performed preoperatively and postoperatively. An anaphylactic reaction was defined as major changes from baseline within 10 min of aprotinin administration of systolic pressure 20% or greater, heart rate 20% or greater, inspiratory pressure greater than 5 cm H2O, or a skin reaction. RESULTS: In 121 cases (71 adults, 46 children), a mean aprotinin reexposure interval of 1,654 days (range, 16-7,136 days) was observed. Preoperative antiaprotinin IgG (optical density ratio > 3) and IgE antibodies (radioallergosorbent test [RAST] score < 3) were detected in 18 and 9 patients, respectively. High concentrations of each (IgG, optical density ratio > 10; IgE, RAST score > or = 3) were detected in five patients. Three patients (2.5%; 95% confidence interval, 0.51-7.1%) experienced an anaphylactic reaction after aprotinin exposure, followed by full recovery; these patients had reexposure intervals less than 6 months (22, 25, and 25 days) and the highest preoperative IgG concentrations of all patients (P < 0.05). Assay sensitivity was 100%, as no anaphylactic reactions occurred in IgG-negative patients (95% confidence interval, 0.0-3.1%); assay specificity was 98%. Preoperative IgE measurements were quantifiable in two of three reactive patients and in three nonreacting patients. CONCLUSIONS: Quantitative detection of antiaprotinin IgE and IgG lacks specificity for predictive purposes; however, quantitation of antiaprotinin IgG may identify patients at risk for developing an anaphylactic reaction to aprotinin reexposure.

Rapid binding of a cationic active site inhibitor to wild type and mutant mouse acetylcholinesterase: Brownian dynamics simulation including diffusion in the active site gorge.

It is known that anionic surface residues play a role in the long-range electrostatic attraction between acetylcholinesterase and cationic ligands. In our current investigation, we show that anionic residues also play an important role in the behavior of the ligand within the active site gorge of acetylcholinesterase. Negatively charged residues near the gorge opening not only attract positively charged ligands from solution to the enzyme, but can also restrict the motion of the ligand once it is inside of the gorge. We use Brownian dynamics techniques to calculate the rate constant kon, for wild type and mutant acetylcholinesterase with a positively charged ligand. These calculations are performed by allowing the ligand to diffuse within the active site gorge. This is an extension of previously reported work in which a ligand was allowed to diffuse only to the enzyme surface. By setting the reaction criteria for the ligand closer to the active site, better agreement with experimental data is obtained. Although a number of residues influence the movement of the ligand within the gorge, Asp74 is shown to play a particularly important role in this function. Asp74 traps the ligand within the gorge, and in this way helps to ensure a reaction.

Specific considerations with the automatic implantable atrial defibrillator.

INTRODUCTION: Internal atrial defibrillation has been evaluated as an alternative approach to the external technique for more than two decades. Previous studies in animals and humans have shown that internal atrial defibrillation is feasible with relatively low energies. The promising results achieved with internal atrial defibrillation have facilitated the development of an implantable atrial defibrillator (IAD). METHODS AND RESULTS: For any new therapy, it is imperative to demonstrate safety, efficacy, tolerability with improvement in quality of life, and cost-effectiveness compared with therapeutic options already available. Maintenance of sinus rhythm or prolonged duration in arrhythmia-free intervals should be demonstrated clearly with an IAD. Initial clinical experience with the Metrix system indicates stable atrial defibrillation thresholds, appropriate R wave synchronization markers, no shock-induced ventricular proarrhythmia, and excellent detection of atrial fibrillation (AF) with a specificity of 100%. Ventricular proarrhythmia has not been reported for correctly R wave synchronized low-energy shocks when closely coupled to RR intervals, and long-short cycles are avoided. CONCLUSION: Preliminary experience with the Metrix system suggests that the IAD may offer a therapeutic alternative for a subgroup of patients with drug-refractory, symptomatic, long-lasting, and infrequent episodes of AF. Further efforts must be undertaken to reduce the patient discomfort associated with internal atrial defibrillation in an attempt to make this new therapy acceptable to a larger patient population with AF.

[Löffler fibroblastic endocarditis in the thrombotic stages in isolated right ventricular tissue eosinophilia]. / Endokarditis fibroplastica Löffler im thrombotischen Stadium bei isolierter rechtsventrikulärer Gewebe-Eosinophilie.

We report on a male, 31 year old, Turkish patient with an intracardiac mass in the right ventricle, reduction of performance and weight, as well as intermittent fever. No eosinophilia was documented in the peripheral blood; cardiac function was primarily normal. Besides the differential diagnosis of Löffer's endocarditis (endomyocardial fibrosis) an inflammatory disease and a malignant cardiac tumor were suggested. The diagnosis of Löffler's endocarditis could not be confirmed morphologically by echocardiography nor histologically by right ventricular biopsy. Operative removal of the mass lesion was necessary because of fast tumor progression, fulminant pulmonary embolism, and infiltration of the tricuspid valve. Only then, histologically Löffler's eosinophilic endocarditis of thrombotic stage was diagnosed. Antiphlogistic therapy with cortisone was initially performed. With a dose reduction after 6 months, a relapse of the thrombotic mass occurred. Therefore, continuous treatment with cortisone and azathioprine was induced followed by further tumor regression and further clinical stabilization since 8 months of treatment.

Electrostatic influence on the kinetics of ligand binding to acetylcholinesterase. Distinctions between active center ligands and fasciculin.

To explore the role that surface and active center charges play in electrostatic attraction of ligands to the active center gorge of acetylcholinesterase (AChE), and the influence of charge on the reactive orientation of the ligand, we have studied the kinetics of association of cationic and neutral ligands with the active center and peripheral site of AChE. Electrostatic influences were reduced by sequential mutations of six surface anionic residues outside of the active center gorge (Glu-84, Glu-91, Asp-280, Asp-283, Glu-292, and Asp-372) and three residues within the active center gorge (Asp-74 at the rim and Glu-202 and Glu-450 at the base). The peripheral site ligand, fasciculin 2 (FAS2), a peptide of 6.5 kDa with a net charge of +4, shows a marked enhancement of rate of association with reduction in ionic strength, and this ionic strength dependence can be markedly reduced by progressive neutralization of surface and active center gorge anionic residues. By contrast, neutralization of surface residues only has a modest influence on the rate of cationic m-trimethylammoniotrifluoroacetophenone (TFK+) association with the active serine, whereas neutralization of residues in the active center gorge has a marked influence on the rate but with little change in the ionic strength dependence. Brownian dynamics calculations for approach of a small cationic ligand to the entrance of the gorge show the influence of individual charges to be in quantitative accord with that found for the surface residues. Anionic residues in the gorge may help to orient the ligand for reaction or to trap the ligand. Bound FAS2 on AChE not only reduces the rate of TFK+ reaction with the active center but inverts the ionic strength dependence for the cationic TFK+ association with AChE. Hence it appears that TFK+ must traverse an electrostatic barrier at the gorge entry imparted by the bound FAS2 with its net charge of +4.

Epicardial neodymium. YAG laser photocoagulation of ventricular tachycardia without ventriculotomy in patients after myocardial infarction.

BACKGROUND: Surgical ablation of ventricular tachycardia (VT) after myocardial infarction has been reported by different endocardial approaches. The ventriculotomy may increase mortality of the procedure. METHODS AND RESULTS: We report on nine patients who suffered from recurrent VT in the late post-myocardial infarction period. Significant stenoses were detected in all patients. The mean left ventricular ejection fraction was 43.1 +/- 8.3%. Left ventricular scar (n = 9) was seen. The mean NYHA class was 2.2 +/- 0.4. Sustained VT (mean cycle length, 293 +/- 52 ms) occurred spontaneously (n = 9) and could be induced reproducibly. Catheter mapping detected a prematurity of -42 +/- 13 ms in six patients. Clinical VT was inducible during surgery in seven patients. Middiastolic potentials were detected from the epicardial surface (n = 3), and premature potentials were found (n = 8 with prematurity of -108 +/- 46 ms). Application of neodymium/yttrium/argon/ garnet (Nd:YAG) laser energy to early epicardial activation terminated the arrhythmia (n = 7). Ventriculotomy was not performed. Seven patients have been free of VT for a mean follow-up period of 17 +/- 11 months; one patient relapsed and was treated with an implantable cardioverter-defibrillator, as was a second patient with inducible VT after surgery. CONCLUSIONS: Surgical Nd:YAG laser photocoagulation of VT on the epicardial surface of the heart in post-myocardial infarction patients without ventriculotomy is safe and has a high success rate. At the present time, this method is recommended in patients with sustained and tolerated VT who need bypass surgery. This is the first report on epicardial laser ablation of VT in post-myocardial infarction VT.

Cisapride reduces postoperative gastrocaecal transit time after cardiac surgery in children.

OBJECTIVE: To investigate the influence of the prokinetic drug cisapride on gastrocaecal transit time (GCTT) in children after open heart surgery. DESIGN: Prospective, randomized and controlled study. SETTING: Interdisciplinary paediatric intensive care unit in a tertiary-care children's hospital. PATIENT: Twenty-one children with a median age of 6.2 years on day 1 after uncomplicated open heart surgery for isolated septal defects, acquired mitral or aortic valve disease or tetralogy of Fallot. Control group consisting of 10 healthy children with a median age of 8.1 years. INTERVENTIONS: Ten children were randomized to receive cisapride 0.2 mg/kg body weight, 30 min prior to measurement of GCTT. MEASUREMENTS AND RESULTS: GCTT was measured using hydrogen breath testing with a test solution containing lactulose and mannitol (0.4 g/kg and 0.1 g/kg body weight respectively). GCTT was markedly delayed in all patients compared to the control group. Within 8 h 8/10 patients in the treatment group versus 4/11 patients in the non-cisapride group achieved gastrocaecal transit. No adverse side-effects were observed. CONCLUSIONS: Cisapride accelerates gastrocaecal transit after open heart surgery in children. In intensive care patients on inotropic support or opioid medication, it may facilitate the earlier reintroduction of enteral feeding.