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During a study period from 1985 through 1988, plasma von Willebrand's factor antigen (vWF:Ag) concentration was measured as a marker for prevalence of the von Willebrand's disease (vWD) trait in Doberman Pinschers (doberman, n = 5,554), Scottish Terriers (scottie, n = 1,363), and Shetland Sheepdogs (sheltie, n = 4,279). Significant increase in prevalence of the trait was seen in scotties and shelties during this period. In 1988, 73% of dobermans, 30% of scotties, and 28% of shelties tested had abnormal vWF:Ag concentration (less than 50% vWF:Ag). We found significant differences between breeds with respect to age and vWF:Ag concentration of clinically affected dogs at time of diagnosis. The affected dobermans were older (doberman mean age, 4.6 years; scottie mean age, 1.7 years; sheltie mean age, 1.9 years) and had higher concentration of plasma vWF:Ag (doberman mean vWF:Ag, 15%; scottie mean vWF:Ag, 0%; sheltie mean vWF:Ag, 8%). Bleeding in affected dogs of all 3 breeds was observed predominantly from mucosal surfaces and from cutaneous sites of surgery or trauma. The most common site of mucosal bleeding in scotties and shelties was oral or nasal cavity, and in dobermans was the urogenital tract. Differences in clinical manifestations of vWD in purebred dogs may reflect heterogeneous defects within the vWF gene, causing a variety of abnormalities in production, structure, and function of vWF protein. Analogous to vWD in human beings, acquired deficiencies of vWF may also contribute to the clinical variability of vWD in dogs.
Detailed viscosity measurements have been made of barium sulfate mixtures over a wide range of viscosities for use in radiography of the esophagus, stomach, and duodenum. A new methodology was developed for more accurate estimation of viscosity in non-Newtonian fluids in conventional cylinder-type viscometers. As base cases, the variation of viscosity with shear rate was measured for standard commercial mixes of e.z.hd (250% w/v) and a diluted mixture of liquid e.z.paque (40% w/v). These suspensions are strongly shear thinning at low shear rates. Above about 3s-1 the viscosity is nearly constant, but relatively low. To increase the viscosity of the barium sulfate mixture, Knott's strawberry syrup was mixed to different proportions with e.z.hd powder. In this way viscosity was systematically increased to values 130,000 times that of water. For these mixtures the variation of viscosity with temperature, and the change in mixture density with powder-syrup ratio are documented. From least-square fits through the data, simple mathematical formulas are derived for approximate calculation of viscosity as a function of mixture ratio and temperature. These empirical formulas should be useful in the design of "test kits" for systematic study for pharyngeal and esophageal motility, and clinical analysis of motility disorders as they relate to bolus consistency.
Abrupt esophageal distention occurs commonly during gastroesophageal reflux, thereby generating a circumstance favorable to esophagopharyngeal regurgitation and laryngeal aspiration of gastric refluxate. The aims of the present study were to examine the glottal response to esophageal distention by air and regional esophageal distention by a balloon. Fifteen healthy volunteers (age, 25 +/- 5 years) were studied while they were in an upright position. Using concurrent videoendoscopy and manometry, glottal and upper esophageal sphincter (UES) responses to abrupt esophageal distention by air injection (10-60 mL) and balloon distention (1.5, 2.0, and 2.5 cm) were recorded simultaneously. In addition, 6 subjects were studied with concurrent synchronized videofluoroscopy. Results showed that esophageal distention by air at a threshold volume of 10-60 mL caused vocal cord closure. The UES response to this threshold volume was variable. Volumes larger than the threshold value caused complete UES relaxation and belching. In addition to vocal cord closure, belching was accompanied by anterior movement of the glottis. On videofluoroscopy, the hyoid bone moved anteriorly in association with belching, but not with vocal cord closure without belching. Proximal esophageal distention by the balloon also provoked vocal cord closure. This response was less consistent for balloon distention in the middle and distal esophagus. It is concluded that (a) esophageal distention by either air or a balloon evokes a glottal closure mechanism, thereby suggesting the existence of an esophagoglottal reflex; (b) this reflex is elicited most easily by distention of the proximal esophagus; (c) glottal and UES responses to esophageal distention are independent from each other; and (d) the esophagoglottal closure reflex may play an important role in preventing laryngeal aspiration of acid due to gastroesophageal reflux accompanied by acid regurgitation into the pharynx.
Some patients with achalasia have been reported to develop airway obstruction from a massively air-distended esophagus, which may represent an abnormality in the upper esophageal sphincter belch reflex. When questioned carefully, 95% of our achalasia patients reported difficulty with belching. The upper esophageal belch reflex in 23 consecutive achalasia patients and 12 healthy controls was studied using an upper esophageal sphincter sleeve manometry catheter and rapid injection of 20-50 mL of air into the midesophagus. Compared with normal subjects, achalasia patients were significantly less likely to have an esophageal belch for all volumes tested and were more likely to have an increase rather than a decrease in upper esophageal sphincter pressure in response to air injection. This study systematically documents that many achalasia patients have an alteration in the upper esophageal sphincter belch reflex that may be a contributory mechanism for some of the chest and upper airway symptoms reported by some patients during acute esophageal distension.
Pharyngeal coordination, sphincter opening, and flow pressures during swallowing were investigated in patients with pharyngeal (Zenker's) diverticula. Fourteen patients with diverticula and 9 healthy age-matched controls were studied using simultaneous videoradiography and manometry. Pharyngeal and upper esophageal sphincter pressures were recorded by a perfused side hole/sleeve assembly. Temporal relationships among swallowing events, extent of sphincter opening during swallowing, and intrabolus pressure during bolus passage across the sphincter were measured. The timing among pharyngeal contraction and sphincter relaxation, opening, and closure did not differ between patients and controls. Sphincter opening was significantly reduced in patients compared with controls in sagittal (P = 0.0003) and transverse (P = 0.005) planes. Manometric sphincter relaxation was normal in patients. Intrabolus pressure was significantly greater in patients than in controls (P = 0.001). It is concluded that Zenker's diverticulum is a disorder of diminished upper esophageal sphincter opening that is not caused by pharyngosphincteric incoordination or failed sphincter relaxation. Incomplete sphincter opening is likely to cause dysphagia. Increased hypopharyngeal pressures during swallowing are probably important in the pathogenesis of the diverticulum.
The oesophageal acid clearance time was evaluated in 10 healthy volunteers of 'small' boluses of 0.5 and 1 ml and 'minute' boluses of 0.05 and 0.1 ml 0.1 N HCl, as well as 0.1 and 1 ml 0.01 and 0.001 N HCl. Swallow rate was normalised at q 60 seconds. For 0.1 ml 0.1 N HCl, acid clearance time was also measured for swallow intervals of q 30 and 120 seconds. Acid clearance time to restore pH to 4.0 was significantly longer (p less than 0.01) for the 0.5 and 1 ml 0.1 N HCl (210 and 273 seconds, respectively) than for the 0.05 and 0.01 ml acid boluses (83 and 94 seconds, respectively). The minimum acid clearance time was 18 seconds (0.05 ml 0.1 N HCl). Acid clearance time for 0.1 N HCl was less than one minute on only two occasions. The acid clearance times were comparable when the subjects sat upright. A longer interswallow interval--that is, 120 seconds, resulted in a significantly longer acid clearance time than shorter swallow intervals (p less than 0.05). Oesophageal acid clearance time for small acid volumes averaged more than three minutes and for minute acid volumes was generally more than one minute; and acid clearance times were comparable for the supine and upright postures, while gastrooesophageal reflux episodes causing pH drops to 3-4 may last for less than 15 seconds, substantial oesophageal pH drops to less than or equal to 1.5 that persists less than 15 seconds are difficult to be attributed to true gastrooesophageal reflux.
The aim of the present study was to 1) characterize nicotine-induced peristalsis in the feline esophagus and 2) determine the site of action of nicotine. Experiments were done on ketamine-sedated cats. Esophageal contractions were measured using a multilumen catheter assembly system. After recording 1 degree and 2 degrees peristaltic sequences nicotine (50-100 micrograms/kg iv) was administered. Nicotine induced a peristaltic contraction through the esophageal striated and smooth muscle part of the esophagus, which was not associated with any mylohyoid electromyogram activity or pharyngeal response, although the upper esophageal sphincter did relax. Addition of either atropine (20-50 micrograms/kg iv) or hexamethonium (10-20 mg/kg iv), a peripherally acting nicotinic antagonist, did not affect the striated muscle portion of the nicotine-induced esophageal contractile response but antagonized the smooth muscle response. However, mecamylamine (0.5-1 mg/kg iv), a ganglionic antagonist that crosses the blood-brain barrier, abolished the esophageal response to nicotine. Succinylcholine (0.5-1 mg/kg iv) abolished the striated muscle response without affecting the nicotine-induced smooth muscle contractility. Finally, the nicotine-induced peristaltic sequence was abolished after bilateral cervical vagotomy. In conclusion, nicotine, administered peripherally, activates central brain stem mechanisms that mediate a peristaltic sequence through the feline esophagus.
The mechanisms of airway protection, upper esophageal sphincter (UES) opening, and their coordination during belching were studied with a concurrent videoendoscopic, videofluoroscopic, and manometric technique. Analysis of videoendoscopic recordings revealed that glottal function during gastric and esophageal belching was similar and consisted of vocal cord adduction resulting in closure of intoitus to trachea, followed by anterior-caudad movement of the glottis, followed by slitlike or triangular UES opening. When a belch episode was associated with an intragastric pressure increase, in addition to the above features, there was approximation of arytenoids to the base of the epiglottis before the UES opened. Duration of vocal cord closure during belches induced by 40 ml intraesophageal air injection was significantly longer than belches induced by 20 ml (P less than 0.01). Vocal cord closure preceded the UES opening invariably. Analysis of videofluoroscopic recordings showed that hyoid bone movement during belching had a distinctive pattern different from its movement during swallowing. UES opening started generally when the hyoid bone was pulled anteriorly. Anterior hyoid excursion of 0.78 +/- 0.1 cm during belching was significantly shorter than its excursion of 1.8 +/- 0.09 cm during swallowing (P less than 0.01). We conclude that glottal closure is an integral component of both esophageal and gastric belch reflexes that prevents aspiration of regurgitated material into the airway. Glottal closure mechanism during belching has two tiers of closure: 1) vocal cord closure and 2) aryepiglottic approximation. Glottal and UES functions are closely coordinated during belching, and finally, during belching, UES is pulled open after its relaxation.
Events associated with gastroesophageal reflux have been determined by concurrent diaphragmatic and esophageal body electromyography, video radiography, and manometry in four conscious dogs. Three characteristic phenomena occurred in parallel immediately before and during gastroesophageal reflux: 1) transient lower esophageal sphincter relaxation, 2) profound (99.5%) and selective inhibition of crural diaphragmatic activity, and 3) a previously unrecognized dorsal movement of the gastroesophageal junction (mean 1.3 cm) demonstrated by implanted radiological markers. The patterns associated with spontaneous acid and gas reflux were indistinguishable from those induced by gastric distension. Costolumbar diaphragmatic activity was stable up until the instant of sphincter opening, when there was a single costolumbar contraction of short duration and high amplitude. Esophageal shortening did not occur before reflux. Reflux that occurred after atropine-induced inhibition of lower esophageal sphincter tone to < 2 mmHg was intermittent and coincided with selective crural inhibition. These studies demonstrated that selective crural inhibition is a prerequisite for gastroesophageal reflux and suggest that the crural diaphragm is an important factor for the maintenance of gastroesophageal competence.
The effects of aging, tachypnea, bolus volume, and chronic obstructive pulmonary disease on the coordination of swallowing with the phases of respiration were studied by concurrent respirography and submental surface electromyography. Study findings showed that in young healthy volunteers, during rest, there is preferential coupling of subconscious swallowing with the expiratory phase of continuous respiration. This preferential coupling of swallowing with expiration was found to increase relative to other phases of respiration during water swallows and tachypnea (P < 0.05). Respiratory phase occurrence of swallowing and postdeglutitive resumption of respiration during exacerbation of chronic obstructive pulmonary disease was found to be significantly different compared with the basal state (P < 0.05). Respiratory phase occurrence of subconscious swallowing in the elderly was found to be different from the young (P < 0.05). Position had no significant effect on the coordination of swallowing and phases of respiration. We concluded that in resting young volunteers the majority of deglutitions are coupled with the expiratory phase of swallowing. This coupling is increased in frequency by the presence of a liquid bolus and tachypnea. And finally, age and chronic obstructive pulmonary disease alter this coordination significantly.
We studied the propagation of phasic contractions initiated by tetraethylammonium (TEA, 1-10 mM), high K+ concentration (10-30 mM), and bethanechol (10(-6) to 10(-2) M) in a whole organ in vitro preparation of the opossum smooth muscle esophagus. TEA initiated phasic contractions that began at all sites along the smooth muscle esophagus and propagated in both directions with a velocity similar to that of primary peristalsis. Blockade of neural transmission by tetrodotoxin (TTX, 10(-7) M) did not prevent contraction propagation. Although a majority of contractions initiated by TEA did not propagate the full length of the esophageal specimen, with the addition of TTX most contractions initiated by TEA did propagate the full specimen length in either direction. High K+ concentration and bethanechol elicited propagated contractions similar to those initiated by TEA. We conclude that 1) a myogenic mechanism exists for propagation of contractions along the smooth muscle esophagus and 2) intramural inhibitory nerves modulate the extent of myogenic propagation in the ascending as well as descending direction. We suggest that esophageal peristalsis may occur by myogenic propagation of contractions that are normally initiated in the proximal smooth muscle esophagus by excitatory nerves. Intramural inhibitory nerves may inhibit retrograde propagation as well as mediate descending inhibition in advance of the peristaltic wave.
This two-phase experiment assessed the effects over time of a solution containing 1.09% sodium fluoride, .40% stannous fluoride, and .14% hydrogen fluoride (.717% fluoride solution, DentinBloc) on pain associated with dentinal hypersensitivity. During phase I, 30 subjects demonstrating dentinal hypersensitivity to a blast of cool air were divided into three double blind experimental groups. After baseline data were collected for all subjects, one group was instructed to apply the .717% fluoride solution twice a day. A second group was instructed to apply a gel containing .04% stannous fluoride (Gel-Kam) twice a day. A third group was instructed to apply distilled water. Each subject was assessed at 2, 4, 8, and 16 weeks utilizing the "method of limits" with a standardized, repeatable cold thermal stimulus. The results of a two factor repeated ANOVA indicated that those subjects who applied the .717% fluoride solution reported significantly less sensitivity at the 2-week period than the other groups (P < .05). In addition, those subjects whose solution contained the 0.4% stannous fluoride reported significantly less sensitivity at the 4- to 8-week periods (P < .05). Phase II of the study assessed the .717% fluoride solution on a more precise time course. These included: immediately, 15 minute, 1 day, 1 week and 2 weeks. A one factor repeated ANOVA revealed that this effect presented 15-minute post application (P < .05) and continued throughout the testing periods. It was concluded that the fully active 0.717% fluoride solution was an effective agent in the control of dentinal hypersensitivity after two 1-minute applications.
A modified double-sandwich enzyme-linked immunosorbent assay (ELISA), which was developed for human and canine von Willebrand's factor (vWF), was adapted for quantitation of vWF in other species. In addition to human and dog plasmas, 12 other mammalian plasmas that were surveyed exhibited significant cross-species reactivity with antibodies specific for canine vWF or monoclonal antibodies against porcine or bovine vWF. Mixed combinations of monoclonal antibodies and various polyclonal antibodies were also used as sandwich or capture antibodies. The ability of this multispecies ELISA to detect less than 0.002 U of vWF per milliliter of plasma in a large number of species enhances its utility for both research and clinical diagnostic applications. A quantitative assay for rabbit vWF, which exhibits poor cross-species reactivity with most antibodies, was constructed with anti-porcine monoclonal antibody W1-5 and goat-anti-canine vWF as capture and sandwich antibodies, respectively. The same conjugate antibody configuration was used to visualize rabbit vWF multimers by immunoblotting. Specificity of the assay for vWF in human, dog, pig, and horse plasmas was confirmed by use of species-specific vWF-deficient plasmas. In other species, for which vWD plasmas were not available, ELISA specificity for vWF was demonstrated by recovery of greater than 75% of the ELISA-reactive antigen coincident with vWF multimers in the high-molecular-weight (greater than 500 kd) fractions of purified plasmas. This multispecies ELISA permits, for the first time, the measurement of vWF in a variety of mammals for which species-specific immunologic reagents do not currently exist. The results also suggest that certain vWF epitopes have been highly conserved among phylogenetically diverse species.
Bleeding diathesis in a Quarter Horse filly was caused by von Willebrand disease. Hemorrhage occurred mainly from mucosal surfaces and after trauma. Quantitative and qualitative measurements of plasma von Willebrand factor (vWF) documented a specific deficiency of vWF high molecular weight multimers, and concurrently greater than expected deficiency of vWF activity relative to vWF concentration. These findings are characteristic of type-II von Willebrand disease in human beings. Application of vWF assays used in human and small animal medicine now permits evaluation of vWF and diagnosis of von Willebrand disease in horses with bleeding disorders.
Factor XII deficiency and impaired prekallikrein activity were diagnosed in a 1-year-old Chinese Shar Pei. The dog experienced repeated episodes of intestinal hemorrhage and diarrhea. Laboratory findings were compatible with blood loss (iron deficiency anemia and hypoproteinemia). Necropsy findings suggested mild infiltrative bowel disease that could have been responsible for the dog's diarrhea, but no explanation for the severe recurrent gastrointestinal hemorrhage could be found. Factor XII deficiency is uncommon in the dog and is not associated with hemorrhagic tendencies. The factor XII deficiency in this case may have contributed to the gastrointestinal hemorrhage.
Using a minimally compliant infusion system and a triple-lumen pressure recording catheter, we obtained endoscopic manometric measurements from both the common bile duct and pancreatic duct segments of the sphincter of Oddi (SO) in 58 patients. Fifteen patients (ages 27-69) had the diagnosis of functional abdominal pain, 19 patients (ages 30-76) had partial biliary obstruction, and 24 patients (ages 15-80) had idiopathic acute recurrent pancreatitis. Resting ductal pressure was similar in the common bile duct and pancreatic duct in all patient groups. In the group with functional pain, basal SO pressure was similar, whether obtained from the common bile duct or pancreatic duct sphincteric segment. Eight of 19 patients with partial biliary obstruction had elevated basal SO pressure. Five of these eight patients had elevated basal SO pressure confined exclusively to the common bile duct segment of the sphincter, while three patients had elevated basal SO in both segments. Conversely seven of 24 patients with acute recurrent pancreatitis had an elevated basal SO pressure, with five patients having pressure elevation only in the pancreatic duct segment while two patients had abnormal basal SO pressure in both segments. We conclude that selective cannulation of the common bile duct and/or the pancreatic duct during manometric study of the SO is necessary in order to diagnose segmental SO dysfunction responsible for partial biliary obstruction or episodes of acute recurrent pancreatitis.
A unified discussion of the mechanics of the swallowing process, and its interpretation through manometric measurements of intraluminal pressure, are presented in this paper. The goals of the discussions are to provide the reader with basic knowledge of pharyngeal, esophageal, and sphincter mechanics; to relate the mechanical processes to intraluminal pressure recordings; and to clarify the relationship between intraluminal pressure and esophageal muscle contractile behavior. The esophageal phase of bolus transport, in particular, is discussed in some detail due to the relatively simple geometry and the straightforward description of peristalsis and muscle mechanics in this region. Several important issues are emphasized in the discussion. For example, pressure variation within a static bolus is fundamentally different from that within a moving bolus. Manometric recordings must be interpreted accordingly. The importance of differentiating between "hydrodynamic pressure," which is pressure measured within a fluid bolus, and "contact pressure," which is the direct squeeze of the luminal wall on the manometric port in a region devoid of bolus fluid, is discussed in some detail. We argue that pressure "amplitude" does not, in principle, give any indication of the forces required to drive the fluid bolus forward. What should be sought is the variation of intrabolus pressure relative to the contact pressure, particularly during periods in which the contractile segment fails to obliterate the esophageal lumen. Examples of intraluminal pressure recording in the esophagus, using manometry and mathematical models, are presented to demonstrate both the possibilities and the difficulties of interpreting manometric recordings in the absence of concurrent radiographic imaging. We discover that in regions of nearly complete luminal closure, the pressure signature and bolus geometry are strongly coupled during peristaltic transport, providing the possibility that in these regions quantitative measures of muscle performance might be developed without the need for radiographic imaging. On the other hand, the ambiguity in the interpretation of manometric recordings that often accompanies dysphagic conditions suggests that as more sophisticated interpretations are sought, manometry concurrent with radiography will play a more prominent role in patient evaluation.