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Clinical experience suggests that granulation tissue may be inhibited by coverage with a musculocutaneous flap. We hypothesized that coverage of an open wound with a musculocutaneous flap would result in regression and apoptosis of the wound's granulation tissue.In the first experiment, 32 rats underwent excisional wounding; 16 underwent musculocutaneous flap coverage of their granulation tissue on postwounding day 8, and then 16 rats (8 controls + 8 flaps) were killed on both postwounding days 10 and 12 (2 and 4 days after the flap procedure, respectively). In the second experiment, 18 rats were wounded, and on postwounding day 5 the rats underwent flap coverage (n = 6), wound edge release/mobilization (the first step of the flap procedure) without flap coverage (n = 6), or dressing change only (n = 6); all rats were killed on postwounding day 6 (24 hours after the secondary intervention). Apoptosis was quantified with the terminal deoxynucleotidyl transferase-mediated nick-end labeling assay.Placement of a musculocutaneous flap over an 8-day-old excisional wound in the first experiment increased the apoptotic rate in the granulation tissue from 0% to 1% (controls) to 5% to 10% at both 2 and 4 days after flap coverage (P.05). Cell population density decreased 50% in the flap-covered granulation tissue compared with the controls (P.05). In the second experiment, circumferential release of the granulation tissue resulted in an equivalent increase in granulation tissue apoptosis over controls compared to that induced by the full flap procedure.Coverage of established granulation tissue with a musculocutaneous flap resulted in histologic regression of the wound's granulation tissue after 2 to 4 days of flap coverage and induced at least a 5-fold increase in the apoptotic rate of the granulation tissue. Releasing the wound edge increased granulation tissue apoptosis to a level equivalent to that produced by the musculocutaneous flap procedure, suggesting that alteration of the wound's mechanical environment is responsible for the acute induction of apoptosis in this model.

Despite the economic slowdown, the profitability of the U.S. commercial banking industry remained high in 2001. Although the weak economy contributed to a sharp rise in provisions for loan and lease losses, those losses were offset in large part by an advance in realized gains on investment account securities as banks' portfolios benefited from declining short- and intermediate-term market interest rates. Profits were also supported by reductions in noninterest expense, as large merger-related charges in 2000 were not repeated last year. Lower short-term interest rates also spurred a rapid increase in core deposits, which provided banks with plentiful, low-interest-rate funding. The expansion of bank balance sheets was slower in 2001 than in the preceding year, as weaker economic activity held down growth in loans to businesses. Loans to households advanced relatively rapidly, though at a somewhat slower pace than in 2000. An increase in the share of banks' portfolios consisting of mortgage-backed securities issued by government agencies, which have lower risk weights than loans, together with continued strong earnings, contributed to an increase in risk-based capital ratios.

The number of antireflux procedures performed for gastroesophageal reflux disease in the United States has increased in the past decade. In a sampling of US hospitals by the National Center for Health Statistics, the number of patients discharged with the International Classification of Disease (ICD-9-CM) classification 44.66 (“Other procedures for creation of esophagogastric sphincteric competence,” ie, fundoplication) in the years 1988, 1993, and 1998 was 13,000, 22,000, and 40,000, respectively. It would be safe to say that the majority of these antireflux procedures are now minimally invasive. The trend for more laparoscopic antireflux procedures also has been seen in Europe. The current approach of choice for surgical treatment of gastroesophageal reflux disease is a minimally invasive transabdominal antireflux procedure. During this evolution of operational approach there have been untoward events associated with the minimally invasive antireflux operation. There is a growing need to audit the results of minimally invasive antireflux procedures because there has been (in the medical literature) a question of its efficacy, and also because of the development of novel endoscopic procedures to reproduce a sphincter mechanism in the lower esophagus, which potentially could compete with laparoscopic antireflux surgery. In this review the results of primary laparoscopic antireflux procedures will be examined (international experience, English-language literature) with an emphasis placed on the description of perioperative complications and primary procedure failures. Data on redo procedures also will be analyzed to determine the causes for failure of primary minimally invasive procedures. Recommendations for avoiding the complications and failure of the primary minimally invasive antireflux procedure will be described.

We hypothesized that pituitary adenylate cyclase-activating polypeptide (PACAP) activates intracardiac postganglionic parasympathetic nerves and has a different effect than cervical vagal stimulation. We measured effective refractory period (ERP) and conduction velocity at four atrial sites [high right atrium (HRA), low right atrium (LRA), high left atrium (HLA), and low left atrium (LLA)] and minimum atrial fibrillation (AF) cycle length at 12 atrial sites during cervical vagal stimulation and after PACAP in 26 autonomically decentralized, open-chest, anesthetized dogs. PACAP shortened ERP to a similar extent at all four sites (HRA, 58 +/- 2.0 ms; LRA, 60 +/- 6.3 ms; HLA, 68 +/- 11.5 ms; and LLA, 60 +/- 8.3 ms). Low- and high-intensity vagal stimulation shortened ERP at the HRA, but not in the other atrial sites (low-intensity stimulation: HRA, 64 +/- 4.0 ms; LRA, 126 +/- 5.1 ms; HLA, 110 +/- 9.5 ms; and LLA, 102 +/- 11.5 ms; high-intensity stimulation: HRA, 58 +/- 4.2 ms; and HLA, 101 +/- 4.0 ms). Conduction velocity was not altered by any intervention. Minimum AF cycle length after PACAP was similar in both atria but was shorter in the right atrium than in the left atrium during vagal stimulation. After atropine administration, no interventions changed ERP. These results suggest that PACAP shortens atrial refractoriness uniformly in both atria through activation of intrinsic cardiac nerves, not all of which are activated by cervical vagal stimulation.

The response to major burn injury includes systemic release of mediators that may have an effect on wound healing. The authors evaluated the effect of a burn injury on the contraction of an excisional wound adjacent to the burn, and the effect of plasma derived from burn-injured animals on the contraction of the fibroblast-populated collagen matrix (FPCM). Nine rats (90-100 days old) under anesthesia received a standardized 40% total body surface area burn to the dorsum, and eight rats (controls) were sham burned. Immediately thereafter all animals had a square (2.25 cm2) of unburned dermis excised from the dorsum, superior to the burn wound. The excisional wound area was measured at 2 to 3-day intervals postoperatively. Plasma was collected from some animals on postburn day 15; the contraction-stimulating ability of burn vs. control plasma was measured in the FPCM. All animals remained free of sepsis. The excisional wound area in all animals decreased to 50% and then 25% of the initial area after approximately 4 and 8 days respectively. The rate of wound contraction (i.e., wound area reduction) did not differ between burn and control animals. Contraction stimulated by 5% plasma in the FPCM (expressed as a percentage of the original matrix area) was 70.2+/-6.4 (standard deviation) mm2 vs. 62.4 +/-3.9 mm2 for burn vs. control rats respectively (p>0.05). Burn injury in this model did not alter the contraction of an excisional wound at an unburned site. There was no significant difference in the contraction-stimulating ability (FPCM model) of plasma from the burned rats compared with plasma from unburned control rats. Burn injury appears to have an inconsequential effect on the contraction of an adjacent wound.

Maintenance of sinus rhythm is the primary goal of antiarrhythmic drug therapy for recurrent atrial fibrillation (AF). However, concern about proarrhythmic and negative inotropic effects has led to increasing reluctance to administer antiarrhythmic agents for this non-life-threatening arrhythmia. Moricizine is well tolerated in a wide variety of patients, and therefore, may be a safe and effective agent for treating AF. We retrospectively assessed the efficacy and safety of moricizine (mean dose 609 +/- 9 mg/day) in 85 consecutive patients with recurrent AF (2.6 +/- 0.5 years duration, 1.6 +/- 1 failed antiarrhythmic drugs). Structural heart disease was present in 69 (81%), but no recent myocardial infarct (< or =90 days) was present; mean left atrial size was 46 +/- 1 mm, and mean left ventricular ejection fraction was 0.51 +/- 0.01. Moricizine was discontinued because of unsuccessful direct-current cardioversion (n = 5) or clinically unacceptable side effects (n = 6); 6 patients developed transient side effects not requiring discontinuation. Of the 74 patients continuing therapy, 68% remained in sinus rhythm after 6 months, and 59% after 12 months. During a follow-up (21 +/- 2 months), there were neither deaths nor adverse effects requiring discontinuation of therapy. Thus, moricizine was effective, safe, and well tolerated in our patient cohort with AF.

A patient undergoing laparoscopic Nissen fundoplication had an intraoperative finding of a left Bochdalek hernia, which was repaired with an onlay of fenestrated PTFE. This appears to be the first report of such a case.

Background/Aims: Primary repair of a large hiatal hernia is associated with a published recurrence rate of up to 10%; anecdotal rates even higher than this have been reported to the authors. The use of prosthetic material in the repair of other abdominal wall defects has often produced better results than primary repair. We wanted to compare laparoscopic primary repair of large hiatus hernias with laparoscopic primary repair reinforced with prosthetic. Methods: Thirty-one patients with symptomatic gastroesophageal reflux and a hiatal defect 8 cm or greater were randomized to Nissen fundoplication with posterior cruroplasty (n = 16) or Nissen cruroplasty, and onlay of polytetrafluoroethylene (PTFE) mesh (n = 15). All patients underwent preoperative esophagogastroduodenoscopy (EGD) and barium esophagography. After posterior cruroplasty with interrupted nonabsorbable suture, the mesh reinforcement group had an onlay of PTFE placed around the hiatus. A radial slit with 3 cm ‘keyhole’ (to accommodate the esophagus) was cut into the PTFE. The prosthetic was stapled to the diaphragm, and the two leaves of the slit were stapled to each other. All patients underwent EGD at 3 months and all had esophagrams every 6 months postoperatively. Follow-up ranged from 12 to 36 months. Results: Length of hospital stay was equal in both groups (2 days). The average cost to the patient with PTFE was USD 1,050 higher than to the patient with primary repair. There were 2 complications (1 pneumonia, 1 urinary retention) in the PTFE group, and 1 complication (pneumothorax) in the primary repair group. There were 3 recurrences (18.8%) in the primary group (p = 0.08, χ2 test). Conclusion: The use of PFTE reinforcement for primary repair of large hiatal hernias may result in a lower rate of recurrent herniation compared to primary repair alone.

Sinoatrial Parasympathetic Innervation. Introduction: The response to sinoatrial parasympathetic nerve stimulation (shortened atrial refractoriness) was used to determine the atrial distribution of these nerve fibers in humans. We hypothesized that, in humans, parasympathetic nerves that innervate the sinoatrial node also innervate the right atrium and that the greatest density of innervation is near the sinoatrial nodal fat pad. Methods and Results: Temporary epicardial wire electrodes were sutured in pairs in the sinoatrial nodal fat pad, high right atrium, and right ventricle by direct visualization during coronary artery bypass surgery in nine patients. Appropriate electrode placement was confirmed by electrically stimulating the fat pad in the operating room to prolong sinus cycle length by 50%. Experiments were performed in the electrophysiology laboratory 1 to 5 days after surgery. Programmed atrial stimulation was performed via an endocardial electrode catheter advanced to the right atrium. The catheter tip electrode was moved in 1-cm concentric zones around the epicardial wires by fluoroscopic guidance. Atrial refractoriness was determined in the presence and absence of sinoatrial parasympathetic nerve stimulation at each cutheter site. In 8 of 9 patients, parasympathetic nerve stimulation reproducibly prolonged sinus cycle length by 50%. There was no effect on AV nodal conduction (no prolongation of PR interval) and no change in AV nodal refractoriness. Atrial effective refractory periods reproducibly shortened in response to parasympathetic nerve stimulation in 1-cm zones up to 3 cm surrounding the fat pad, by a mean (± SEM) of 26.6 ± 4.3 msec (zone 1), 11.4 ± 1.8 msec (zone 2), and 10.0 ± 2.5 msec (zone 3), respectively (P = 0.0001). At distances > 3 cm from the fat pad, the effective refractory period did not shorten. Conclusion: Stimulation of parasympathetic nerves that innervate the sinoatrial node shortened atrial refractoriness in humans.

Background —Ventricular tachyarrhythmias present a unique set of stimuli to arterial and cardiopulmonary baroreceptors by increasing cardiac filling pressures and decreasing arterial pressure. The net effect on the control of sympathetic nerve activity (SNA) in humans is unknown. The purpose of this study was to determine the relative roles of cardiopulmonary and arterial baroreceptors in controlling SNA and arterial pressure during ventricular pacing in humans. Methods and Results —Two experiments were performed in which SNA and hemodynamic responses to ventricular pacing were compared with nitroprusside infusion (NTP) in 12 patients and studied with and without head-up tilt or phenylephrine to normalize the stimuli to either the arterial or cardiopulmonary baroreceptors in 9 patients. In experiment 1, the slope of the relation between SNA and mean arterial pressure was greater during NTP (−4.7±1.4 U/mm Hg) than during ventricular pacing (−3.4±1.1 U/mm Hg). Comparison of NTP doses and ventricular pacing rates that produced comparable hypotension showed that SNA increased more during NTP ( P =0.03). In experiment 2, normalization of arterial pressure during pacing resulted in SNA decreasing below baseline ( P P =0.04). Conclusions —These data demonstrate that in humans arterial baroreflex control predominates in mediating sympathoexcitation during ventricular tachyarrhythmias and that cardiopulmonary baroreceptors contribute significant inhibitory modulation.

OBJECTIVES To evaluate whether use of beta-adrenergic blocking agents, alone or in combination with specific antiarrhythmic therapy, is associated with improved survival in persons with ventricular fibrillation (VF) or symptomatic ventricular tachycardia (VT). BACKGROUND The ability of beta-blockers to alter the mortality of patients with VF or VT receiving contemporary medical management is not well defined. METHODS Survival of 1,016 randomized and 2,101 eligible, nonrandomized patients with VF or symptomatic VT followed in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial through December 31, 1996 was assessed using Cox proportional hazards analysis. RESULTS The 817 (28%) patients discharged from hospital receiving beta-blockers had less ventricular dysfunction, fewer symptoms of heart failure and a different pattern of medication use compared with patients not receiving beta-blockers. Before adjustment for important prognostic variables, beta-blockade was not significantly associated with survival in randomized or in eligible, nonrandomized patients treated with specific antiarrhythmic therapy. After adjustment, beta-blockade remained unrelated to survival in randomized or in eligible, nonrandomized patients treated with amiodarone alone (n = 1142; adjusted relative risk [RR] = 0.96; 95% confidence interval [CI] 0.64-1.45; p = 0.85) or a defibrillator alone (n = 1347; adjusted RR = 0.88; 95% CI 0.55 to 1.40; p = 0.58). In contrast, beta-blockade was independently associated with improved survival in eligible, nonrandomized patients who were not treated with specific antiarrhythmic therapy (n = 412; adjusted RR = 0.47; 95% CI 0.25 to 0.88; p = 0.018). CONCLUSIONS Beta-blocker use was independently associated with improved survival in patients with VF or symptomatic VT who were not treated with specific antiarrhythmic therapy, but a protective effect was not prominent in patients already receiving amiodarone or a defibrillator.

The choice of suture material is becoming increasingly complex. The multiple factors to consider when choosing a suture for closure of a fascial incision include its handling characteristics, ability to incite an inflammatory reaction, cost, knot security, and susceptibility to in vivo degradation. One of the more important factors to consider when picking a suture is the durability of tensile strength. Currently available sutures are described as rapidly absorbing, slowly absorbing, and nonabsorbable/permanent. These definitions are variable, and even some sutures described as permanent eventually degrade. Probably the most important criterion on which to judge a suture is its role in early and late wound failure (defined here as dehiscence and hernia, respectively). This review will emphasize the evaluation of suture using that criterion.

To evaluate right ventricular abnormalities with magnetic resonance (MR) imaging in patients with arrhythmia but without arrhythmogenic dysplasia.In 53 patients being evaluated for right ventricular arrhythmia and 15 control subjects, MR imaging was performed to evaluate fixed thinning, fatty replacement, or reduced systolic wall thickening or motion. A diagnosis of idiopathic right ventricular outflow tract tachycardia or indeterminate was assigned for each patient, and the severity of arrhythmia was categorized.Right ventricular abnormalities were revealed in 32 (60%) of the 53 patients: fixed thinning in 27 (84%), fatty replacement in eight (25%), and reduced wall thickening or motion in 31 (97%). Right ventricular abnormalities were found in 35 (76%) of 46 patients with idiopathic right ventricular outflow tract tachycardia and in seven (39%) of 18 patients with indeterminate diagnoses (P = .022).Mild right ventricular abnormalities are likely sources for arrhythmias, even in the absence of arrhythmogenic right ventricular dysplasia.

Background . The clinical results of implantable cardioverter-defibrillator (ICD) implantation in the elderly have received limited documentation. As the longevity of the U.S. population has increased, so has the need for ICD implantation in the elderly. We evaluated the efficacy and outcome of ICD implantation in elderly patients (>70 years) compared with younger patients. Methods . The case records of all consecutive patients who underwent ICD implantation at our institution between 1986 and 1994 were reviewed. Of a total of 238 patients, 78 patients were 70 years of age or older and 160 patients were younger than 70 years of age. Results . The mean age of the younger group was 58 years and that of the elderly group was 74 years. There were no statistical differences in the presence of coronary artery disease, left ventricular systolic function, the inducibility of arrhythmias, or the history of sudden cardiac death. The hospital morbidity rate was similar in both groups (6.9% in the younger group and 7.7% in the elderly group; p = not significant). The operative mortality rate was 1.9% for the younger group and 1.3% for the elderly group ( p = not significant). At a mean follow-up of 33 ± 26 months, Kaplan-Meier survival curves demonstrated similar survival rates, with 93%, 82%, and 65% of the patients alive at 1, 3, and 6 years, respectively. Conclusions . Implantable cardioverter-defibrillator implantation was equally effective in the treatment of patients older than 70 years as in younger patients. No differences in theoretic survival or morbidity were observed.

Tilt-table testing after therapy with beta blockade is frequently used to predict clinical success. This study found that heart rate and blood pressure reductions after beta-blocker therapy did not predict the results of the follow-up tilt-table test, but low blood pressure at rest before the initial test predicts failure of this therapy.

background It is a common belief that a laparoscopic procedure results in a shorter duration of postoperative ileus compared with the equivalent open procedure. This study was undertaken to determine whether laparoscopically assisted right hemicolectomy in the dog results in a shorter duration of ileus compared with open right hemicolectomy. methods Eight bipolar serosal electrodes (4 on the small bowel, 4 on the left colon) were implanted in each dog (n = 10). Three weeks after electrode implantation baseline recording was made for 5 days; then 5 dogs underwent laparoscopically assisted right hemicolectomy and 5 underwent open right hemicolectomy. Myoelectric activity was recorded continuously for 72 hours postoperatively. Tracings were analyzed for the time of reappearance, duration, migration velocity, and cycle length of phase 2, phase 3, and the migrating colonic complex. The criteria used for the resolution of postoperative ileus were the return of phase 2, phase 3, and the migrating colonic complex. results: All dogs had temporary loss of organized myoelectric activity postoperatively. The mean reappearance time (minutes±standard deviation) for phase 3 was 857±574 versus 761±600; the phase 2 reappearance time was 1,845±610 versus 1,590±668; and the migrating colonic complex reappearance time was 534±365 versus 57252, open versus laparoscopically assisted right hemicolectomy, respectively. The times were not different (Wilcoxon rank sum test, P > 0.05). The time required for phase 3, phase 2, and the migrating colonic complex to attain preoperative configuration also was not different between the open and laparoscopically assisted group. conclusion Myoelectric resolution of postoperative ileus did not occur earlier in the dog undergoing laparoscopically assisted right hemicolectomy compared to the dog undergoing open right hemicolectomy. This data does not support the hypothesis that a laparoscopically assisted colectomy results in a shorter duration of postoperative ileus than the equivalent open procedure.

Patients with nifedipine-induced gingival hyperplasia (GH) often require continued calcium channel blocker therapy. Switches to diltiazem and verapamil have been described; however, these drugs are of a different chemical class and present therapeutic limitations in some patients. The purpose of this study was to evaluate the effect on nifedipine-induced GH of a switch to a dihydropyridine derivative with a low incidence of GH. Fourteen patients with nifedipine-induced GH were given a medical exam and a periodontal exam. The following parameters were assessed: probing depth (PD), gingival margin (GM), gingival thickness (GT), plaque index (PI), and gingival index (GI). Intraoral photographs, study models, and a gingival biopsy for histological examination were taken. Following baseline measures, patients were randomized to continued treatment with nifedipine or an equivalent dose of isradipine in a single-blind fashion. Biweekly periodontal parameters were taken for 8 weeks. At the end of 8 weeks, some patients elected to receive 4 weeks of open label isradipine therapy, with biweekly examination continuing through the open label phase. The isradipine treatment arm showed a mean decrease in PD of 0.59 mm at week 8 (P < 0.05). No other measured parameter (GM, GT, PI, GI) was significantly changed, compared either to baseline or to the alternate treatment arm. Clinically, 60% of patients treated with isradipine exhibited a decrease in hyperplasia, while 66% of patients treated with nifedipine demonstrated an increase in hyperplasia, a significant difference (P < 0.05). When combined with open label data, patients switching therapy to isradipine exhibited an increase in GM (increase in recession) of 0.74 mm from baseline to week 12 (P < 0.05). No patients treated with isradipine exhibited an increase in gingival overgrowth. All patients exhibited adequate control of hypertension. We conclude that in hypertensive patients with nifedipine-induced GH, switching hypertensive therapy to isradipine may result in a regression of GH. When coupled with aggressive oral hygiene treatment, this drug may provide a reasonable option for patients requiring dihydropyridine treatment.

Laparoscopic highly selective (anterior and posterior) vagotomy was performed in 11 patients for duodenal ulcer (n = 10) and duodenal ulcer with prepyloric ulcer (n = 1). All patients were endoscoped both pre- and postoperatively. There were no perioperative complications. The average operating time was 3.2 ± 0.4 hours and the average hospital stay was 1.7 ± 0.2 day (range 1 to 3 days). None of the patients required parenteral narcotics postoperatively. The patients have been followed for 6 months to 5 years after operation. All ulcers healed as demonstrated by endoscopy. There was one recurrence at 9 months in a patient who had a prepyloric ulcer preoperatively. The recurrence was treated successfully with medication. There has been no other long-term morbidity. Laparoscopic highly selective vagotomy is feasible, safe, requires a brief hospital stay, and produces short-term results comparable with open surgery.

A general surgeon closes thousands of abdominal incisions during a typical career, and most surgeons do this quite well. It would be presumptuous to say that this article delineates the technique of wound creation and closure that all surgeons should adopt to minimize acute wound failure. The search for the optimal laparotomy technique has gone on for more than 100 years and will continue. Contained here is a review of what has been studied and what is believed to be true regarding acute wound failure; an opinion is given on which methods currently seem best to avoid and manage this problem.

Three types of minimally invasive ventral herniorrhaphies were performed in eight patients: primary repair with sutures (1 case), single-layer prosthesis repair with polytetrafluoroethylene (4 cases), and bilayer prosthesis repair with polytetrafluoroethylene and polypropylene (3 cases). One patient undergoing the bilayer repair developed a small hematoma in the subcutaneous tissue at the site of the repair, which resolved without intervention. There were no other complications, and no recurrence was noted in follow-up of 14 to 20 months.

Neurocardiogenic syncope is a general term that describes syncope resulting from altered autonomic activity, as manifested by abnormal regulation of peripheral vascular resistance and heart rate. Although there has been great interest in the contribution of heart rate to this form of syncope, the peripheral circulation plays the dominant role in the induction of neurocardiogenic syncope in most patients. We review in this brief article the physiology of cardiovascular reflexes, which are important for short-term arterial pressure control, and their potential contribution to the pathophysiology of neurocardiogenic syncope. This type of syncope represents a profound failure of the normal mechanisms for short-term regulation of arterial pressure. Any therapeutic strategies for the management of neurocardiogenic syncope must deal with alterations in vascular control, which contribute to its pathogenesis.

Background. Intravenous amphotericin B (AMB) administration in animals causes renal vasoconstriction, ischemia, and oliguria that may result in irreversible renal injury; the mechanism of AMB nephrotoxicity may be similar in human beings. Adenosine is excreted in urine by the ischemic kidney. We hypothesized that adenosine excretion and oliguria would be a marker for patients who later would manifest AMB-associated renal insufficiency and that pre-AMB saline administration (which ameliorates AMB nephrotoxidty) would negate the change in adenosine excretion and urine output. Methods. Twenty hospitalized patients being treated at the direction of their attending physician and who were receiving AMB (15 to 75 mg intravenously) had urine collected for 1 hour before and for 2 hours during AMB infusion. Eleven patients received normal saline solution (500 ml intravenously) before the AMB infusion; the other nine formed the comparator group. An aliquot of each urine collection was precipitated with perchloric acid to remove protein and cellular elements and centrifuged, and the supernatant was assayed for adenosine by using high-pressure liquid chromatography. Results. Infusion of AMB was associated with a decrease in mean urine output both in patients who received saline solution (245 before versus 149 ml/hr during AMB infusion, p = 0.04) and in patients in comparator group (139 versus 89 ml/hr, p = 0.027). The mean urinary adenosine excretion was unchanged in the saline-loaded group (0.1354 before versus 0.1255 mmol/hr during drug infusion, p = 0.25) and was decreased in the comparator group (0.2276 versus 0.1127 mmol/hr, p = 0.01). Development of renal insufficiency did not correlate with the change in urine output or adenosine excretion. Conclusions. AMB infusion in human beings results in decreased urine output and decreased adenosine excretion. The latter effect is prevented by a pre-AMB saline load. The changes in urine output and adenosine excretion are not predictive of the development of renal insufficiency.

A case of gastric outlet obstruction secondary to peptic ulcer disease was treated with laparoscopic truncal vagotomy and Jaboulay gastroduodenostomy. The technique is described.

An injury to a side branch of the inferior vena cava (IVC) was incurred during laparoscopic right adrenalectomy. The hemorrhage was controlled with the aid of a laparoscopic balloon retractor, and laparotomy was avoided.

Experimentally, distal mutations in myoglobin substantially affect the contribution of fast and slow phases to picosecond geminate recombination of NO following flash photolysis. Earlier simulations of ligand diffusion among distal pocket mutants showed greatly differing rates of collisions between the ligands and the heme iron, suggesting that distal residues affect recombination by controlling ligand access to the iron [Gibson, Q. H., Regan, R., Elber, R., Olson, J. S., & Carver, T. (1992) J. Biol. Chem. 267, 22022-22034). In this work, molecular dynamics simulations of sperm whale myoglobin and mutations at positions 68 (E11) and 107 (G8) have been examined to investigate the structural mechanism that controls ligand diffusion and iron accessibility. Visualization of the distal ligand-accessible spaces shows a pattern of cavities (common to other hemoglobins and myoglobins) that fluctuate and interconnect due to protein motions. Access to the iron atom is highly sensitive to these fluctuations in the native structure, perhaps a reason for the strong conservation of distal residues. The positions of the helices surrounding the distal heme site were monitored to assess the involvement of more collective protein motions in ligand diffusion. Ligand migrations and collisions with the iron appear related to expansion of the distal protein matrix due to helix movements. The helices surrounding the distal site also make relative adjustments on the order of 0.5 A to accommodate the presence of a mobile diatomic ligand, suggesting a mechanism for communication between the heme site and the exterior of the protein.

The operative and short-term results of 29 patients who had an open fundoplication were compared to 36 patients who had a laparoscopic fundoplication. The operative time was 2.8 +/- 0.4 and 3.1 +/- 0.3 h for the open and laparoscopic procedure, respectively. The length of hospital stay was 9.2 +/- 0.7 days for the open and 1.8 +/- 0.2 days for the laparoscopic. There were five complications in the open group and one in the laparoscopic group. The follow-up period was 3-32 months and all patients had a barium swallow and esophago-gastroduodenoscopy (EGD) for postoperative evaluation. All patients had resolution of esophagitis on follow-up endoscopy, were free of reflux symptoms, and no longer required antireflux medication. Laparoscopic Nissen fundoplication has an operative time that is comparable to the open procedure. The complication rate for laparoscopic fundoplication is acceptable. Patients undergoing a laparoscopic fundoplication have a shorter hospital stay compared to patients with an open procedure. The short-term outcome for the laparoscopic fundoplication group was excellent.

Gastric bypass and vertical banded gastroplasty are the two procedures used most frequently in the treatment of morbid obesity. In a pilot study, we used a porcine model in which laparoscopic gastric stapling and Roux-en-Y gastrojejunostomy were accomplished.

High-resolution structures of the aquomet, deoxy, and CO forms of Ala68, Ile68, Leu68, and Phe68 sperm whale myoglobins have been determined by X-ray crystallography. These 12 new structures, plus those of wild-type myoglobin, have been used to interpret the effects of mutations at position 68 and the effects of cobalt substitution on the kinetics of O 2 , CO, and NO binding. Molecular dynamics simulations based on crystal structures have provided information about the time-dependent behavior of photolyzed ligands for comparison with picosecond geminate recombination studies. The Val68→Ala mutation has little effect on the structure and function of myoglobin. In Ala68 deoxymyoglobin, as in the wild-type protein, a water molecule hydrogen-bonded to the N e atom of the distal histidine restricts ligand binding and appears to be more important in regulating the function of myoglobin than direct steric interactions between the ligand and the C γ atoms of the native valine side-chain. This distal pocket water molecule is displaced by the larger side-chains at position 68 in the crystal structures of Leu68 and Ile68 deoxymyoglobins. The Leu68 side-chain can rotate about its C α –C β and C β –C γ bonds to better accommodate bound ligands, resulting in net increases in overall association rate constants and affinities due to the absence of the distal pocket water molecule. However, the flexibility of Leu68 makes simulation of picosecond NO recombination difficult since multiple starting conformations are possible. In the case of Ile68, rotation of the substituted side-chain is restricted due to branching at the β carbon, and as a result, the δ methyl group is located close to the iron atom in both the deoxy and liganded structures. The favorable effect of displacing the distal pocket water molecule is offset by direct steric hindrance between the bound ligand and the terminal carbon atom of the isoleucine side-chain, resulting in net decreases in affinity for all three ligands and inhibition of geminate recombination which is reproduced in the molecular dynamics simulations. In Phe68 myoglobin, the benzyl side-chain is pointed away from the ligand binding site, occupying a region in the back of the distal pocket. As in wild-type and Ala68 myoglobins, a well-defined water molecule is found hydrogen bonded to the distal histidine in Phe68 deoxymyoglobin. This water molecule, in combination with the large size of the benzyl side-chain, markedly reduces the speed and extent of ligand movement into the distal pocket. Ligand movement away from the iron atom is also reduced dramatically by the Phe68 side-chain, causing large and rapid geminate recombination phases for all ligands.

To the Editor: Product quality is our highest priority at St. Jude Medical (SJM). To ensure accuracy and address misperceptions, we are providing responses to assertions in the Perspective article by Hauser in this issue of the Journal.1 Assertion: Recommendations for following patients with Riata silicone-only leads for implantable cardioverter–defibrillators (ICDs) are not based on meaningful data, and SJM has not instituted clinical studies. Facts: We have conducted extensive bench and short-term studies, and on the basis of the scientific data and clinical experience, in which 85% of externalized conductors in returned leads functioned normally, we have worked with . . .

Ventricular arrhythmias occur in up to 13.5% of patients after tetralogy of Fallot repair. We describe a patient with a 30-year history of recurrent ventricular tachycardia, which followed the surgical repair of tetralogy of Fallot. Findings at electrophysiological study were consistent with reentry involving an area of slow conduction in the right ventricular outflow tract. Following the transcatheter application of radiofrequency energy in the right ventricular outflow tract, ventricular tachycardia could no longer be induced and has not occurred spontaneously during follow-up (28 months). Thus, transcatheter radiofrequency ablation is an acceptable therapeutic option in some patients with ventricular tachycardia after the surgical repair of tetralogy of Fallot.

Impedance Mismatch Causes Conduction Block. Introduction: The impedance mismatch hypothesis has been proposed as one of the mechanisms responsible for accessory connection conduction block. Methods and Results: We describe a case in which retrograde conduction across block posters accessory connection was ablated at the atrial insertion site in the coronary sinus of, whereas Anterograde conduction was ablated at the ventricular insertion site in the left ventricle. Conclusion: The evidence supports the impedance mismatch concept as the cause of unidirectional conduction block and shows that the distal junction between the accessory connection and the myocardium is more vulnerable to ablation.

Human induced pluripotent stem (hiPS) cells offer a novel source of patient-specific cells for regenerative medicine. However, the biological potential of iPS-derived cells and their similarities to cells differentiated from human embryonic stem (hES) cells remain unclear. We derived fibroblast-like cells from two hiPS cell lines and show that their phenotypic properties and patterns of DNA methylation were similar to that of mature fibroblasts and to fibroblasts derived from hES cells. iPS-derived fibroblasts (iPDK) and their hES-derived counterparts (EDK) showed similar cell morphology throughout differentiation, and patterns of gene expression and cell surface markers were characteristic of mature fibroblasts. Array-based methylation analysis was performed for EDK, iPDK and their parental hES and iPS cell lines, and hierarchical clustering revealed that EDK and iPDK had closely-related methylation profiles. DNA methylation analysis of promoter regions associated with extracellular matrix (ECM)-production (COL1A1) by iPS- and hESC-derived fibroblasts and fibroblast lineage commitment (PDGFRβ), revealed promoter demethylation linked to their expression, and patterns of transcription and methylation of genes related to the functional properties of mature stromal cells were seen in both hiPS- and hES-derived fibroblasts. iPDK cells also showed functional properties analogous to those of hES-derived and mature fibroblasts, as seen by their capacity to direct the morphogenesis of engineered human skin equivalents. Characterization of the functional behavior of ES- and iPS-derived fibroblasts in engineered 3D tissues demonstrates the utility of this tissue platform to predict the capacity of iPS-derived cells before their therapeutic application.

Scholars differ on whether central bank intervention mitigates banking panics. In April 1929, a fruit fly infestation in Florida forced the U.S. government to quarantine fruit shipments from the state and destroy infested groves. In July, depositors panicked in Tampa and surrounding cities. The Federal Reserve Bank of Atlanta rushed currency to member banks beset by runs. We show that this intervention arrested the panic and estimate that bank failures would have been twice as high without the Federal Reserve’s intervention. Our results suggest that similar interventions may have reduced bank failures during the Great Depression.

The mechanism of vasovagal syncope during orthostasis in humans is unknown. Opioid receptors have been implicated in the vasovagal-like responses to hemorrhagic hypotension in conscious animals. We sought to determine if opioid receptor blockade with naloxone (μ receptor antagonist) would prevent or delay the onset of vasovagal syncope in humans. Three protocols were performed in which heart rate, arterial pressure, sympathetic nerve activity, thoracic impedance and forearm vascular resistance were measured during stepwise steady-state increments of lower body negative pressure (LBNP) in nine healthy volunteers. In protocol 1, duplicate trials of LBNP to syncope or −60 mmHg were performed with a 30–45 minute rest period separating the trials. No significant differences in any physiologic responses or cumulative stress tolerance were found. In protocol 2, graded LBNP was repeated after administration of saline or naloxone (0.1 mg/kg) in six subjects in which vasovagal syncope occurred prior to −60 mmHg LBNP. The peak increase of sympathetic nerve activity during LBNP was augmented after naloxone ( P = 0.02), but the occurrence of vasovagal syncope was not prevented nor was the cumulative stress tolerated affected ( P = 0.42). The heart rate and arterial pressure responses to LBNP were not affected by naloxone. Similarly, in protocol 3, naloxone given just prior to the onset of pre-syncopal symptoms did not alter the physiologic response or the occurrence of vasovagal syncope. These data show that naloxone does not prevent or delay the onset of vasovagal syncope in humans which suggests that μ opioid receptors do not mediate the vasovagal response.

Signal-averaged electrocardiography (SAECG) is a useful tool for determining which patients are at risk for sustained ventricular tachycardia. 1–3 In patients at risk for sustained ventricular tachycardia, SAECG often shows high-frequency and low-amplitude electrical activity at the terminal portion of the QRS complex. 4–6 This electrical activity is thought to be due to slow conduction in scarred or abnormal ventricular myocardial tissue and is usually not apparent on the standard 12-lead surface electrocardiogram. 7–10 During atrial flutter, flutter waves may occur before, during or after ventricular systole. Atrial flutter waves that occur during ventricular diastole frequently appear as “sawtooth” waves on the standard 12-lead electrocardiogram, particularly in the inferior limb or anterior chest leads. However, atrial flutter waves that occur during ventricular systole may be obscured by the QRS complex. To test the hypothesis that atrial flutter waves that coincide with the terminal portion of the QRS complex cause low-amplitude electrical activity and thus result in a pseudo late potential on the electrocardiogram, we performed SAECG in 9 patients during atrial flutter and normal sinus rhythm.

Prophylactic antibiotics can decrease the incidence of postoperative wound infections in indicated procedures. The accepted indications for administering prophylactic antibiotics have been clean-contaminated procedures and prosthesis insertion, but new indications are evolving that consider wound contamination together with anesthetic risk and relative duration of the operation. A prophylactic antibiotic is chosen on the basis of its activity against endogenous flora likely to be encountered, its toxicity, and its cost, in that order. Potent antibiotics used for serious infections are generally not used for prophylaxis. A maximum dose of a prophylactic antibiotic is given preoperatively so that effective tissue concentration is present at and after the time of incision. In the absence of infection, antibiotics should not be continued beyond the operative day. Regimens for specific procedures are discussed.

Sudden cardiac arrest (SCA) is the most common cause of death in the Unites States. Despite its major impact on public health, significant challenges exist at the patient, provider, public, and policy levels with respect to raising more widespread awareness and understanding of SCA risks, identifying patients at risk for SCA, addressing barriers to SCA care, and eliminating disparities in SCA care and outcomes. To address many of these challenges, the Duke Center for the Prevention of Sudden Cardiac Death at the Duke Clinical Research Institute (Durham, NC) held a think tank meeting on December 7, 2009, convening experts on this issue from clinical cardiology, cardiac electrophysiology, health policy and economics, the US Food and Drug Administration, the Centers for Medicare and Medicaid Services, the Agency for Health Care Research and Quality, and device and pharmaceutical manufacturers. The specific goals of the meeting were to examine existing educational tools on SCA for patients, health care providers, and the public and explore ways to enhance and disseminate these tools; to propose a framework for improved identification of patients at risk of SCA; and to review the latest data on disparities in SCA care and explore ways to reduce these disparities. This article summarizes the discussions that occurred at the meeting.

9024 Background: Vaginal dryness is a common problem, for which effective and safe non-estrogenic treatments are needed. Based on preliminary promising data that pilocarpine attenuated vaginal dryness (Arch Intern Med 159:174-81, 1999), the current trial was conducted. Methods: A double-blind, placebo (PLCB)-controlled, randomized trial design was used to compare pilocarpine, at target doses of 5 mg twice daily and 5 mg four times daily, to a PLCB. Patients (pts) must have had persistent vaginal dryness and/or itching of sufficient severity to desire therapeutic intervention. Vaginal dryness was recorded by pt-completed questionnaires at baseline and weekly for 6 weeks. The primary endpoint was the area under the curve (AUC) summary statistic comprised of the longitudinal responses obtained at baseline and through the 6 weeks of treatment to a 0-10 numerical analogue scale, asking pts to rate their perceived amount of vaginal dryness. The primary analysis was carried out by a single t-test using a two-sid...

While clinical management of patients with ventricular arrhythmias continues to evolve, some basic principles are generally accepted. First, patients with sustained ventricular tachyarrhythmias (ventricular tachycardia or ventricular fibrillation) require treatment. Second, patients with frequent ventricular ectopy or nonsustained ventricular tachycardia in the absence of underlying structural heart disease do not require treatment except when relief of symptoms is warranted. However, the indication for treatment of patients with frequent ventricular ectopy or nonsustained ventricular tachycardia in the presence of underlying structural heart disease remains uncertain. The concern is that these ventricular arrhythmias may be a precursor for sustained, potentially life-threatening ventricular tachyarrhythmias. Available data suggest that patients with underlying structural heart disease, particularly coronary artery disease and a previous myocardial infarction, who manifest frequent ventricular ectopy or more particularly nonsustained ventricular tachycardia, are at increased risk for sudden cardiac death. However, no studies have demonstrated to date that treatment of these arrhythmias will favorably affect outcome. Data are accumulating to suggest that use of the principles of risk stratification permits identification of patients at very high risk for developing sustained ventricular tachyarrhythmias. Carefully designed clinical trials are required before firm guidelines for the management of these patients can be defined.(ABSTRACT TRUNCATED AT 250 WORDS)