Incomplete Relaxation Research Articles

Laparoscopic Anterior Cardiomyotomy Plus Anterior Dor Fundoplication Without Division of Lateral and Posterior Periesophageal Anatomic Structures for Treatment of Achalasia of the Esophagus

Laparoscopic cardiomyotomy is the treatment of choice for patients with achalasia of the esophagus. Several different techniques and modifications have been reported concerning the approach (thoracoscopic or laparoscopic), type and length of the myotomy, with or without fundoplication, type of fundoplication, etc. In this prospective study, we report our simplified technique for anterior cardiomyotomy with Dor fundoplication and the results obtained using this procedure. Only the anterior wall of the esophagus was exposed without dissection of the lateral or posterior periesophageal anatomic structures for the technique. Twenty-five patients were operated by a single surgeon. The diagnosis was based on the clinical, radiologic, endoscopic, and functional esophageal tests. Achalasia was classified into 3 types: achalasia type I was diagnosed in 5 patients, type II in 6 patients, and type III in 14 patients. Manometry demonstrated a mean resting pressure of 33.5 mm Hg (range, 18 to 55), associated with incomplete relaxation. The hospital stay was 3 days; the median operative time was 115 minutes (range, 90 to 150), 2 small mucosal perforations occurred which were immediately sutured during surgery without conversion into open technique and no postoperative complications occurred. After operation, lower esophageal sphincter pressure returned to normal values and complete relaxation in all patients. In type II and III achalasia, the esophageal body diameter decreased more than 50% (P=0.001) compared with the preoperative diameter, and the internal diameter of the esophagogastric junction increased significantly (P=0.001). Only 2 patients presented occasional heartburn and 2 patients received 1 session of hydrostatic dilatation due to mild residual dysphagia. No late recurrence of dysphagia has been observed to the present time (1 to 5 y of follow-up). In conclusion, the goals of the surgery for achalasia are obtained with this simplified technique.

Impaired deglutitive EGJ relaxation in clinical esophageal manometry: a quantitative analysis of 400 patients and 75 controls

Assessing deglutitive esophagogastric junction (EGJ) relaxation is an essential focus of clinical manometry. Our aim was to apply automated algorithmic analyses to high-resolution manometry (HRM) studies to ascertain the optimal method for discriminating normal from abnormal deglutitive EGJ relaxation. All 473 subjects (73 controls) were studied with a 36-channel solid-state HRM assembly during water swallows. Patients were classified as: 1) achalasia, 2) postfundoplication, 3) nonachalasia with normal deglutitive EGJ relaxation, or 4) functional obstruction (preserved peristalsis with incomplete EGJ relaxation). Automated computer programs assessed the adequacy of EGJ relaxation by using progressively complex analysis routines to compensate for esophageal shortening, crural diaphragm contraction, and catheter movement, all potential confounders. The single-sensor method of assessing EGJ relaxation had a sensitivity of only 52% for detecting achalasia. Of the automated HRM analysis paradigms tested, the 4-s integrated relaxation pressure using a cutoff of 15 mmHg performed optimally with 98% sensitivity and 96% specificity in the detection of achalasia. We also identified a heterogeneous group of 26 patients with functional EGJ obstruction attributed to variant achalasia and other diverse pathology. Although further clinical experience will ultimately judge, it is our expectation that applying rigorous methodology such as described herein to the analysis of HRM studies will improve the consistency in the interpretation of clinical manometry and prove useful in guiding clinical management.

Safety of Repeated Courses of Electroconvulsive Therapy in a Patient With Harrington Rods

Although modified electroconvulsive therapy (ECT) may rarely result in musculoskeletal complications, it has also been safely administered to patients with orthopedic morbidity. There is no literature on the safety of repeated courses of ECT in patients with Harrington rod implants. We describe a 30-year-old asthenic bipolar woman who, in 1997, had a Harrington compression assembly stabilizer fitted for spinal tuberculosis and who, between 2000 and 2004, received 3 courses of modified ECT with a total of 28 treatments. In October 2006, she experienced her index episode of mania and was treated with 7 ECTs that were modified with propofol (60 mg) and succinylcholine (0.83 mg/kg). Each ECT seizure was characterized by mild tonic-clonic movements that lasted 20 to 40 seconds. Her mania remitted uneventfully with ECT. Radiological assessment after the ECT course showed that there were no orthopedic complications. Although our patient experienced no musculoskeletal complication despite the incomplete muscle relaxation, for maximum safety, we strongly recommend full muscle relaxation for all patients with orthopedic conditions who are treated with ECT. We also suggest that in such patients, short stimulus durations be used (to the extent possible) to minimize the duration of the tonic muscular contraction that occurs during the passage of the ECT stimulus. With these precautions, the orthopedic risks associated with well-modified ECT may be no greater or less than those associated with a fit of sneezing or coughing. Our report adds to the literature on the safety of modified ECT in patients with orthopedic conditions, such as those with Harrington rods in situ.

A miotomia do cricofaríngeo: artigo de revisão

A miotomia do cricofaríngeo é um procedimento cirúrgico que pode ser indicado para pacientes com disfagia orofaríngea que, em geral, caracterize-se por distúrbio motor limitado à fase faríngea da deglutição, incoordenação cricofaríngea ou relaxamento incompleto do Esfíncter Esofágico Superior (EES). A indicação da miotomia, porém, tem sido discutida e aplicada em muitos casos, sem efeito na melhora da dinâmica da deglutição. O objetivo deste estudo foi verificar os critérios de indicação e eficácia da miotomia do cricofaríngeo, com base nos estudos da fisiologia da deglutição em pacientes com disfagia orofaríngea. Realizou-se, então, uma revisão da literatura sobre este procedimento e a descrição de seus resultados na dinâmica da deglutição. Os resultados demonstraram que os melhores indicadores para uma miotomia bem sucedida são: fase oral eficiente e boa elevação laríngea durante a deglutição. Assim, para uma adequada indicação da miotomia do cricofaríngeo, não se deve avaliar apenas a fase faríngea e o funcionamento isolado do EES, mas a coordenação e relação entre as fases oral e faríngea da deglutição.

Thin Filament Disinhibition by Restrictive Cardiomyopathy Mutant R193H Troponin I Induces Ca 2+ -Independent Mechanical Tone and Acute Myocyte Remodeling

Inherited restrictive cardiomyopathy (RCM) is a debilitating disease characterized by a stiff heart with impaired ventricular relaxation. Mutations in cardiac troponin I (cTnI) were identified as causal for RCM. Acute genetic engineering of adult cardiac myocytes was used to identify primary structure/function effects of mutant cTnI. Studies focused on R193H cTnI owing to the poor prognosis of this allele. Compared with wild-type cTnI, R193H mutant cTnI more effectively incorporated into the sarcomere, where it exerted dose-dependent effects on basal and dynamic contractile function. Under loaded conditions, permeabilized myocyte Ca(2+) sensitivity of tension was increased, whereas the passive tension-extension relationship was not altered by R193H cTnI. Normal rod-shaped myocyte morphology acutely transitioned to a "short-squat" phenotype in concert with progressive stoichiometric incorporation of R193H in the absence of altered diastolic Ca(2+). The specific myosin inhibitor blebbistatin fully blocked this transition. Heightened Ca(2+) buffering by the R193H myofilaments, and not alterations in Ca(2+) handling by the sarcoplasmic reticulum, slowed the decay rate of the Ca(2+) transient. Incomplete mechanical relaxation conferred by R193H was exacerbated at increasing pacing frequencies independent of elevated diastolic Ca(2+). R193H cTnI-dependent mechanical tone caused acute remodeling to a quasicontracted state not elicited by other Ca(2+)-sensitizing proteins and is a direct correlate of the stiff heart characteristic of RCM in vivo. These results point toward targets downstream of Ca(2+) handling, notably thin filament regulation and actin-myosin interaction, in designing therapeutic strategies to redress the primary cell morphological and mechanical underpinnings of RCM.

Resultados inmediatos y tardíos de la miotomía de Heller laparoscópica en pacientes con acalasia esofágica

Achalasia is characterized by an incomplete relaxation of the lower esophageal sphincter. The best treatment is surgical and the laparoscopic approach may have good results. To assess the results of laparoscopic Heller myotomy among patients with achalasia. Prospective study of patients subjected to a laparoscopic Heller myotomy between 1995 and 2004. Clinical features, early and late operative results were assessed. Twenty seven patients aged 12 to 74 years (12 females) were operated. All had disphagia lasting for a mean of 32 months. Mean lower esophageal sphincter pressure ranged from 18 to 85 mmHg. Eight patients received other treatments prior to surgery but symptoms persisted or reappeared. The preoperative clinical score was 7. No patient died and no procedure had to be converted to open surgery. In a follow up of 21 to 131 months, all patients are satisfied with the surgical results and the postoperative clinical score is 1. Only one patient with a mega esophagus maintained a clinical score of six. In this series of patients, laparoscopic Heller myotomy was an effective and safe treatment for esophageal achalasia.

Is aperistalsis with complete lower esophageal sphincter relaxation an early stage of classic achalasia?

Aperistalsis with complete lower esophageal sphincter (LES) relaxation, characterized by the complete relaxation of the LES and aperistalsis of the esophageal body on manometry, has been considered by some authors to be an early manifestation of classic achalasia, which is defined as incomplete relaxation of the LES and aperistalsis of the esophageal body. The aim of the present study was to compare the clinical features of patients with aperistalsis with complete LES relaxation, with those of patients with classic achalasia. Eighteen patients with aperistalsis with complete LES relaxation and 53 patients with classic achalasia were analyzed with regard to clinical history, the maximal diameter of the esophageal body on barium esophagogram, LES resting pressure and the duration of LES relaxation on manometric recordings, and the selected treatment and its efficacy. The aperistalsis with complete LES relaxation group had distinctly different features compared to those of the classic achalasia group including older age, more frequent association with non-cardiac chest pain, less frequent association with dysphagia and weight loss, lower LES resting pressures, and longer duration of LES relaxation. However, the two groups were similar in terms of maximal diameter of the esophageal body, and efficacy associated with pneumatic dilation. Aperistalsis with complete LES relaxation on manometry is not necessarily an early manifestation of classic achalasia. However, this condition does not preclude a diagnosis of achalasia or a good response to achalasia therapy.

Lymphatic vessels transition to state of summation above a critical contraction frequency

Although behavior of lymphatic vessels is analogous to that of ventricles, which completely relax between contractions, and blood vessels, which maintain a tonic constriction, the mixture of contractile properties can yield behavior unique to lymphatic vessels. In particular, because of their limited refractory period and slow rate of relaxation, lymphatic vessels lack the contractile properties that minimize summation in ventricles. We, therefore, hypothesized that lymphatic vessels transition to a state of summation when lymphatic vessel contraction frequency exceeds a critical value. We used an isovolumic, controlled-flow preparation to compare the time required for full relaxation with the time available to relax during diastole. We measured transmural pressure and diameter on segments of spontaneously contracting bovine mesenteric lymphatic vessels during 10 isovolumic volume steps. We found that beat-to-beat period (frequency(-1)) decreased with increases in diameter and that total contraction time was constant or slightly increased with diameter. We further found that the convergence of beat-to-beat period and contraction cycle duration predicted a critical transition value, beyond which the vessel does not have time to fully relax. This incomplete relaxation and resulting mechanical summation significantly increase active tension in diastole. Because this transition occurs within a physiological range, contraction summation may represent a fundamental feature of lymphatic vessel function.

Evolutive Radiological Changes of the Esophagus in Patients with Achalasia Who Did Not Receive Treatment

The radiological features of achalasia of the esophagus are well known and have been described. However, very little is known concerning the natural history of this disease. We aimed to determine the evolutive radiological changes of the esophagus in a group of patients with achalasia who had not previously undergone any treatment. We undertook a prospective study of 14 patients with achalasia from a group of 205 patients. They included 9 women and 5 men who did not receive any treatment at the initial diagnosis. Two radiological parameters were evaluated: (a) the maximal internal diameter of the middle third of the thoracic esophagus in millimeters and (b) the internal diameter of the esophagogastric junction in millimeters. At a mean follow-up of 5-years without any treatment, there was a significant increase in the diameter of the thoracic esophagus, with a rate of "dilatation" of 6.1 mm/year. In addition, there was a significant decrease of the internal diameter of the esophagogastric junction, with a rate of "stenosis" of 1 mm/year. The lower esophageal sphincter was hypertensive in all with an incomplete relaxation. These results suggest that there is a progressive deterioration in the radiological parameters of the esophagus in patients with achalasia not treated over a 5-year period of observation.

Pneumatic dilation or myotomy for achalasia?

Pneumatic dilation or myotomy for achalasia?

Fractal Dimension and Localization of DNA Knots

The scaling properties of DNA knots of different complexities were studied by atomic force microscope. Following two different protocols DNA knots are adsorbed onto a mica surface in regimes of (i) strong binding, that induces a kinetic trapping of the three-dimensional (3D) configuration, and of (ii) weak binding, that permits (partial) relaxation on the surface. In (i) the radius of gyration of the adsorbed DNA knot scales with the 3D Flory exponent nu approximately 0.60 within error. In (ii), we find nu approximately 0.66, a value between the 3D and 2D (nu=3/4) exponents. Evidence is also presented for the localization of knot crossings in 2D under weak adsorption conditions.

Role of transmural pressure and α‐adrenoceptors in acute mechanoadaptive remodeling in mouse tail resistance arteries

After prolonged constriction to norepinephrine, vascular smooth muscle cells (VSMs) undergo a mechanoadaptation process resulting in incomplete relaxation upon removal of the agonist. Experiments were performed to determine the role of transmural pressure (PTM) and α-adrenergic activation in this remodeling. Mouse tail resistance arteries were isolated and exposed to PTMs of 10 or 60 mmHg. A PTM of 60 but not 10 mmHg evoked a robust and prolonged myogenic constriction. Mechanoadaptation and remodeling of VSMs was assessed by recording pressure-diameter relationships in Ca2+-free Krebs solution before and after interventions. Exposure of arterioles to PTMs of 10 or 60 mmHg for 5 min or 4 hrs did not alter the pressure-diameter curves. Arterioles were constricted with norepinephrine (10−6 M, ~50% constriction) for 5 min or 4 hrs at a PTM of 60 mmHg. Constriction to norepinephrine for 5 min did not change the pressure-diameter curves. However, constriction to norepinephrine (10−6 M) for 4 hrs at a PTM of 60 mmHg depressed pressure-diameter curves, and significantly decreased arterial diameter compared with pre-exposure controls (p<0.05). Therefore, α-adrenoceptor stimulation but not the PTM-induced myogenic response causes mechanoadaptive remodeling in mouse tail resistance arteries.

Room temperature photoluminescence evaluation of In0.29Al0.71As/In0.3Ga0.7As/GaAs metamorphic high electron mobility transistor structures

The optical and electrical properties of In0.29Al0.71As/In0.3Ga0.7As/GaAs metamorphic high electron mobility transistor (MM-HEMT) structures grown by molecular beam epitaxy were investigated. The RT PL spectrum shows four peaks, corresponding to In0.29Al0.71As layer grown at 380°C (peak C), In0.29Al0.71As layer grown at 520°C (peak D), the e2–hhl and e1–hhl transitions (the second electron and the first subband to first hole subband) in the channel, respectively. The deviation between peak C and peak D is attributed to In desorption due to high growth temperature, strain resulted from incomplete relaxation of metamorphic InAlAs. The sheet carrier concentration (Ns) and electron mobility (μ) decrease with the deviation increasing, which indicates the electrical properties depend on the quality of metamorphic MM buffers significantly. Therefore, the electrical properties of MM-HEMT can be nondestructively evaluated by room temperature PL spectra.

Does Gastric Banding for Morbid Obesity Reduce or Increase Gastroesophageal Reflux?

Conflicting results regarding the influence of laparoscopic adjustable gastric banding (LAGB) on gastroesophageal reflux disease (GERD) have been published. A prospective follow-up study was conducted in 31 patients (male/female 5/26, mean age 44 +/- 11 SD years) with 24-hour pH and manometry recordings, symptom assessment, and upper GI endoscopy. Total number of reflux episodes decreased from a mean value of 44.6 +/- 23.7 SD preoperatively to 22.9 +/- 17.1 postoperatively (P=0.0006), after a median follow-up time of 19 months (range 7-32 months). Total reflux time decreased from 9.5% +/- 6.2% to 3.5% +/- 3.7%, P=0.0009, and DeMeester score decreased from 38.5 +/- 24.9 to 18.6 +/- 20.4, P=0.03. Symptomatic patients decreased from 48.4% preoperatively to 16.1% postoperatively (P=0.01), medication for GERD decreased from 35.5% to 12.9% (P=0.05), and the diagnosis of GERD on 24-hour pH recordings decreased from 77.4% to 37.5% (P=0.01). There were no pouch enlargements seen on upper GI endoscopy. Esophageal motility was unchanged, but 36% of the patients had incomplete relaxation of the lower esophageal sphincter following the operation (P<0.0001). Mean BMI decreased from 46.0 +/- 5.46 to 38.4 +/- 6.45 (P<0.0001), excess weight from 60.0 kg +/- 18.58 kg, 44.9% +/- 6.56% to 38.4 kg +/- 20.27 kg, 28.4% +/- 10.97% (P<0.0001). No association between the postoperative diagnosis of GERD and the amount of weight loss could be found. The correctly placed gastric band is an effective anti-reflux barrier in the short term. Long-term results have to be awaited.

Power Laws and Non–Power Laws in Dark Matter Halos

Simulated dark matter profiles are often modelled as a `NFW' density profile rather than a single power law. Recently, attention has turned to the rather rigorous power-law behaviour exhibited by the `pseudo phase-space density' of the dark matter halo, which is defined dimensionally in terms of the local density and velocity dispersion of the dark matter particles. The non-power-law behaviour of the density profile is generally taken to exclude simple scale-free, in-fall models; however the power-law behaviour of the `pseudo-density' is a counter indication. We argue in this paper that both behaviours may be at least qualitatively understood in terms of a dynamically evolving self-similarity, rather than the form for self-similar infall that is fixed by cosmological initial conditions. The evolution is likely due to collective relaxation such as that provided by the radial-orbit instability on large scales. We deduce, from a distribution function given by first order coarse-graining, both the NFW-type density profile and the power-law pseudo-density profile. The results are not greatly sensitive to variation about 3 in the power of the velocity dispersion used in the definition of the phase space pseudo-density. We suggest that the power 2 may create the more physical quantity, whose deviations from a power-law are a diagnostic of incomplete relaxation.

Differences in response of the proximal esophagus to wet swallows in patients of Chagas’ disease and idiopathic achalasia

Chagas' disease and idiopathic achalasia have similar esophageal manifestations such as absent or incomplete lower esophageal sphincter relaxation and aperistalsis in the esophageal body (alterations seen mainly in the distal esophageal body). Our aim in this paper was to study the response of the proximal esophageal body to wet swallows in patients with Chagas' disease and patients with idiopathic achalasia. We retrospectively analyzed the time interval between the onset of the pharyngeal contractions 1 cm proximal to the upper esophageal sphincter, as well as 5 cm distal to the pharyngeal measurement. Amplitude, duration and area under the curve of contractions in the proximal esophagus were also determined in 42 patients with Chagas' disease (15 with associated esophageal dilatation), 21 patients with idiopathic achalasia (14 with concomitant esophageal dilatation) and 31 control subjects. The time between the onset of pharyngeal and proximal esophageal contractions was longer in patients with Chagas' disease and in those with esophageal dilatation (1.39 +/- 0.16 s) than in control subjects (0.86 +/- 0.04 s, P < 0.01). The amplitude of proximal esophageal contractions was lower in patients with idiopathic achalasia and esophageal dilatation (60.9 +/- 16.3 mmHg) than in control subjects (89.7 +/- 6.9 mmHg, P = 0.06). The authors conclude that in patients with advanced esophageal disease, the proximal esophageal contractions in Chagas' disease have a delayed response to wet swallows when compared with controls, and that the amplitude of proximal esophageal contractions was lower than expected in patients with idiopathic achalasia.

Relaxation of Surface Stabilised Antiferroelectric Liquid Crystals at Video Frequency

As part of our line of research into high resolution, video rate antiferroelectric displays we have studied the ferroelectric – antiferroelectric relaxation that follows the data pulse, in surface stabilised antiferroelectric liquid crystal (AFLC) displays, driven by biasless or low bias video frequency waveforms. This generally incomplete relaxation reduces the intensity of the light transmitted by a pixel in any partially ferroelectric (grey-level) state during a video frame, and hence limits the frame-averaged brightness of the AFLC display. The relaxation is a function of the surface stabilisation (i.e., the anchoring strength, pre-tilt and thickness of the device and the pitch of the AFLC), the rotational viscosity of the AFLC, the degree of relaxation of the AFLC between successive frames, the magnitude of the data pulse (grey level) and bias voltage. We have optimised the driving scheme for a number of symmetric and asymmetric (biasless) displays with different antiferroelectric materials and a variety of alignment surfaces, and present mathematical fits to the decaying transparency during single frames as functions of the data pulse. Finally we discuss the mechanisms governing the relaxation.

Prolonged Ca 2+ and Force Transients in Myosin RLC Transgenic Mouse Fibers Expressing Malignant and Benign FHC Mutations

Clinical studies have revealed that mutations in the ventricular myosin regulatory light chain (RLC) lead to the development of familial hypertrophic cardiomyopathy (FHC), an autosomal dominant disease characterized by left ventricular hypertrophy, myofibrillar disarray and sudden cardiac death. While mutations in other contractile proteins have been studied widely by others, there is no report elucidating the mechanism(s) associated with FHC-linked RLC mutations. In this study, we have assessed the functional consequences of two RLC mutations, R58Q and N47K, in transgenic mice. Clinical phenotypes associated with these mutations included inter-ventricular hypertrophy, abnormal ECG findings and the R58Q mutation caused multiple cases of premature sudden cardiac death. Simultaneous measurements of the ATPase and force in transgenic skinned papillary muscle fibers from mutated versus control mice showed an increase in the Ca 2+ sensitivity of ATPase and steady-state force only in R58Q fibers. The calculated energy cost or rate of dissociation of force generating myosin cross-bridges (ATPase/force ratio) plotted as a function of activation state was the same in all groups of fibers. Both mutations caused prolonged [Ca 2+] transients in electrically stimulated intact papillary muscles; however, the R58Q mutation also resulted in a significantly prolonged force transient. Our results suggest that the phenotypes of FHC observed in patients harboring these RLC mutations correlate with the extent of physiological changes monitored in transgenic fibers. Cardiac hypertrophy observed in patients is most likely caused by the activation of compensatory mechanisms ensuing from higher workloads due to incomplete relaxation as evidenced by prolonged [Ca 2+] transients for both N47K and R58Q fibers. Furthermore, the poor prognosis of the R58Q patients may be associated with more severe diastolic dysfunction due to the slower off-rate of Ca 2+ from troponin C leading to longer force and [Ca 2+] transients and increased Ca 2+ sensitivity of ATPase and force.

Section 11: Evaluation and Management of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

Section 11: Evaluation and Management of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

Quasi-stationary states and incomplete violent relaxation in systems with long-range interactions

We discuss the nature of quasi-stationary states (QSS) with non-Boltzmannian distribution in systems with long-range interactions in relation with a process of incomplete violent relaxation based on the Vlasov equation. We discuss several attempts to characterize these QSS. We show that their distribution is non-universal and explain why their prediction is difficult in general.