Physiologic mechanism and preoperative prediction of new-onset dysphagia after laparoscopic Nissen fundoplication

The aim of this study was to determine whether preoperative physiologic factors can account for and be used to predict the development of postoperative dysphagia after laparoscopic Nissen fundoplication. One hundred sixty-three patients with gastroesophageal reflux disease underwent laparoscopic Nissen fundoplication with a median follow-up of 14 months (range 6 to 81 months). Preoperative dysphagia was present in 37% (60 of 163) and was relieved in all but five patients (92%). Female sex (P = 0.01) and the presence of a stricture (P = 0.02) were the only preoperative variables associated with the presence of preoperative dysphagia. Eight percent (8 of 103) of patients without preoperative dysphagia developed new-onset dysphagia, and of these 63% (5 of 8) had a normal lower esophageal sphincter (LES) (pressure >6 mm Hg; length >2 cm; abdominal length >1 cm). New-onset dysphagia was significantly more common in patients with a normal LES (22% [5 of 23] vs. 4% [3 of 80], P = 001). Patients with a normal LES had almost a sixfold increase in the risk of developing dysphagia as those with an abnormal LES (relative risk = 5.8). Only a preoperative normal LES (P = 0.02) or mean LES pressures (P = 0.04) were positively associated with the development of postoperative dysphagia. The severity of this dysphagia also showed a strong positive trend of increasing with mean preoperative LES pressures (P = 0.07). Finally, preoperative LES pressure significantly correlated with postoperative LES pressure (r = 0.48, P = 0.01) and with mean residual LES (nadir) pressure (r = 0.33, P = 0.05) offering insight into the mechanism of this dysphagia. In conclusion, preoperative LES parameters play a role in the development of dysphagia after laparoscopic Nissen fundoplication. Patients with a normal LES or high mean LES pressures are at increased risk for developing this complication and should be informed of this before laparoscopic Nissen fundoplication. Presented at the Forty-Second Annual Meeting of The Society for Surgery of the Alimentary Tract, Atlanta, Ga., May 20–23, 2001.     

Weight reduction interventions for persons with a chronic illness: findings and factors for consideration

Obesity in persons with a concomitant chronic illness poses complex issues relating to the choice of appropriate interventions. More recent emphasis on modification of risk factors has resulted in the need to prescribe complex therapeutic regimens with multiple treatment goals. The traditional approach to weight reduction in such persons has been nutrition education. Studies have shown, however, that knowledge alone does not translate into self-care behaviors that in turn result in weight loss and weight maintenance. Although the latter outcomes continue to be primary goals of therapy in obese individuals with a chronic illness, improvement in the physiologic parameters associated with the illness is also a desired outcome. Behavior therapy and group support appear to be enabling factors that go beyond knowledge to facilitate behavior change and subsequent changes in health-related indexes. This article describes various approaches to the problem of combined interventions for patients education and weight reduction. Findings and factors are discussed about whether the primary goal of weight reduction interventions for persons with a chronic illness should focus on pounds lost or improvement in metabolic or physiologic status.     

Shoot First,Draw Later Peroneal Nerve Palsy: A Sonographic Study

A 32–year–old man had an unusual gunshot wound to the leg, causing a peroneal nerve palsy. Sonography provided useful complementary findings to the electrodiagnostic localization of the injury.     

Morphological, neurochemical, and behavioral studies on serotonergic denervation and graft-induced reinnervation of the rat hippocampus.

A procedure was developed to conduct simultaneously immunocytochemical and neurochemical studies on the serotonergic system in adjacent 300-micron-thick slices of rat hippocampus. This procedure was applied to correlate morphological (innervation pattern and density), neurochemical (5-hydroxytryptamine and 5-hydroxyindolacetic acid levels and [3H]5-hydroxytryptamine uptake and release) and behavioral (spatial learning) effects of neurotoxin-induced denervation and reinnervation by grafting fetal mesencephalic raphe cells. Intracerebroventricular injections of a low dose of 5,7-dihydroxytryptamine caused a discrete serotonergic denervation of the hippocampus. Eleven months after lesioning, 5-hydroxytryptamine and 5-hydroxyindolacetic acid levels and [3H]5-hydroxytryptamine uptake capacity were decreased by 50-60%. By this time, the residual fibers displayed an enhanced vulnerability towards K(+)-induced depolarization. Grafting of a fetal raphe cell suspension resulted in a reinnervation of the host hippocampus. The pattern of reinnervation was comparable to control innervation and the density was supranormal at the level of the graft. As observed semiquantitatively, the innervation density decreased with distance from the core of the graft. Neurochemical studies showed that the fibers were capable of synthesizing, metabolizing and releasing 5-hydroxytryptamine. The turnover of 5-hydroxytryptamine in both the denervated and the reinnervated hippocampus was comparable to that in control tissue. Previous behavioral testing of the denervated and of the denervated and implanted animals did not reveal any effect on spatial learning, either in an individual or in a social test paradigm. The latter data substantiate the notion that interference with the hippocampal serotonergic innervation does not hamper adequate spatial learning.     

Release of soluble transferrin receptor from the surface of human leukemic HL60 cells

Information regarding transferrin (Tf) receptor degradation is largely incomplete. HL60 cells were shown to release to their growth medium a Tf-binding protein which could be immunoprecipitated by anti-Tf receptor monoclonal antibodies (MoAbs) B3/25 and OKT9. Soluble Tf receptor was detected in the medium within one hour of replating of cells, and its release was inhibited at 4 degrees C. The affinity of Tf for the soluble receptor released by cells (kd = 2.3 x 10(-10) mol/L) was slightly lower than its affinity for the detergent-solubilized cellular receptor (kd = 1.2 x 10(-10) mol/L). 125I-Tf internalized and released by cells subsequently bound to Tf receptor released by the same cells, and soluble Tf receptor in the conditioned medium (CM) inhibited 125I-Tf binding to intact cells. The soluble Tf receptor isolated from the CM was smaller (78,000 daltons) than the cell surface receptor (94,000 daltons) when analyzed by gel electrophoresis under reducing conditions. Isolated cell membranes readily released soluble receptor; however, this release could be blocked by protease inhibitors. The soluble Tf receptor may represent the extracytoplasmic domain of the cellular Tf receptor released from the surface of HL60 cells through proteolytic cleavage by a membrane-based protease.     

Pneumothorax and other lung diseases: effect of altered resolution and edge enhancement on diagnosis with digitized radiographs

Prior studies have shown that pneumothorax is one of the more difficult entities to diagnose with digitized radiography. This study was designed to test whether increasing resolution from 1.25 to 2.5 line pairs per millimeter (lp/mm) and image processing (edge enhancement from unsharp masking) would increase accuracy and confidence in the diagnosis of pneumothorax, as well as normal cases and other forms of lung disease. Conventional radiographs were digitized with use of a laser reader and then reformatted as film hard copy. Eleven observers read 35 cases reformatted in three different ways (1.25 lp/mm, 2.5 lp/mm, 1.25 lp/mm unsharp mask). The images with finer resolution (2.5 lp/mm) and unsharp mask images were superior to those with coarser resolution (1.25 lp/mm) for the diagnosis of pneumothorax. There was no difference in diagnostic accuracy for normal patients. For abnormalities other than pneumothorax, the unsharp mask images were significantly worse. Confidence in the diagnosis of pneumothorax and other abnormalities was highest with the finest resolution (2.5 lp/mm).     

The pharmacology of GR203040, a novel, potent and selective non-peptide tachykinin NK1 receptor antagonist.

1. The in vitro and in vivo pharmacology of GR203040 ((2S, 3S)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), a novel, highly potent and selective non-peptide tachykinin NK1 receptor antagonist, was investigated in the present study. 2. GR203040 potently inhibited [3H]-substance P binding to human NK1 receptors expressed in Chinese hamster ovary (CHO) and U373 MG astrocytoma cells, and NK1 receptors in ferret and gerbil cortex (pKi values of 10.3, 10.5, 10.1 and 10.1 respectively). GR203040 had lower affinity at rat NK1 receptors (pKi = 8.6) and little affinity for human NK2 receptors (pKi < 5.0) in CHO cells and NK3 receptors in guinea-pig cortex (pKi < 6.0). With the exception of the histamine H1 receptor (pIC50 = 7.5). GR203040 had little affinity (pIC50 < 6.0) at all non-NK1 receptors and ion channels examined. Furthermore, GR203040 produced only weak inhibition of Na+ currents in SH-SY5Y neuroblastoma and superior cervical ganglion cells (pIC50 values < 4.0). GR203040 produced only weak antagonism of Ca(2+)-evoked contractions of rat isolated portal vein (pKn = 4.1). The enantiomer of GR203040, GR205608 (2R, 3R)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), had 10,000 fold lower affinity at the human NK1 receptor expressed in CHO cells (pKi = 6.3). 3. In gerbil ex vivo binding experiments, GR203040 produced a dose-dependent inhibition of the binding of [3H]-substance P to cerebral cortical membranes (ED50 = 15 micrograms kg-1 s.c. and 0.42 mg kg-1 p.o.). At 10 micrograms kg-1 s.c., the inhibition of [3H]-substance P binding was maintained for > 6 h. In the rat, GR203040 was less potent (ED50 = 15.4 mg kg-1 s.c.) probably reflecting, at least in part, its lower affinity at the rat NK1 receptor. 4. In guinea-pig isolated ileum and dog isolated middle cerebral and basilar arteries, GR203040 produced a rightward displacement of the concentration-effect curves to substance P methyl ester (SPOMe) with suppression of the maximum agonist response (apparent pKB values of 11.9, 11.2 and 11.1 respectively). 5. In anaesthetized rabbits, GR203040 antagonized reductions in carotid arterial vascular resistance evoked by SPOMe, injected via the lingual artery (DR10 (i.e. the dose producing a dose-ratio of 10) = 1.1 micrograms kg-1, i.v.). At a dose 20 fold greater than its DR10 value (i.e. 22 micrograms kg-1, i.v.), significant antagonism was evident more than 2 h after GR203040 administration. 6. In anaesthetized rats, GR203040 (3 and 10 mg kg-1, i.v.) produced a dose-dependent inhibition of plasma protein extravasation in dura mater, conjunctiva, eyelid and lip in response to electrical stimulation of the trigeminal ganglion. 7. It is concluded that GR203040 is one of the most potent and selective NK1 receptor antagonists yet described, and as such, has considerable potential as a pharmacological tool to characterize the physiological and pathological roles of substance P and NK1 receptors. GR203040 may also have potential as a novel therapeutic agent for the treatment of conditions such as migraine, emesis and pain.