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Biomedical subjects

W J Dodds

Publications and source records attributed to W J Dodds.

At least 163 records · Page 9Linked to original sources

Effect of selective muscarinic antagonists on peristaltic contractions in opossum smooth muscle.

In this study we examined the role of M1- and M2-muscarinic receptors in the mediation of circular smooth muscle esophageal contractions elicited by pharmacological cholinergic stimulation and during peristalsis in anesthetized opossums. Esophageal-body contractions were induced by bethanechol administration, whereas peristalsis was elicited by pharyngeal stroking or cervical vagal stimulation. Contractions were measured by a low-compliance manometric recording system. The incidence and amplitude of bethanechol-induced contractions were antagonized by 4-diphenylacetoxy-n-methylpiperidine (4-DAMP) and atropine but not pirenzepine. 4-DAMP and atropine caused an increased velocity, decreased amplitude, and preferential reduction of the incidence of primary peristaltic contractions in the proximal smooth muscle esophagus. During long-train vagal stimulation, intra-stimulus A-waves had a velocity similar to primary peristalsis, whereas poststimulus B-waves showed a velocity considerably faster than primary peristalsis. Short-train vagal stimulation produced a contraction sequence, termed an "S-wave," that had a velocity similar to that of the A-wave. At low doses 4-DAMP increased the velocity and decreased the amplitude of A-wave and S-wave contractions, and at high doses 4-DAMP abolished both the A-wave and S-wave contractions. B-wave contractions were minimally affected by 4-DAMP. Pirenzepine had no effect on contractions induced by swallows or vagal stimulation. We conclude that M2-muscarinic receptors mediate esophageal contractions in the circular smooth muscle during primary peristalsis and during A-waves and S-waves induced by vagal stimulation, and M1-receptors do not have any important role in the excitatory neural pathway to the esophagus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Contraction pattern of opossum gallbladder during fasting and after feeding.

Our major aims in this study were to determine in unanesthetized opossums the gallbladder volume, pressure, and tone during fasting as well as after feeding, model the kinetics of changes in gallbladder volume, and correlate gallbladder contractility with concurrent spike burst activity in the upper gastrointestinal tract and sphincter of Oddi (SO). In 10 animals, we implanted electrodes on the gastric antrum, duodenum, SO, and jejunum. An indwelling catheter monitored gallbladder pressure and volume. In two animals, a force transducer sutured to the gallbladder wall monitored gallbladder tone. In each animal, fasting migrating myoelectric complexes (MMCs) were recorded in the stomach and small bowel. Cyclic changes in SO spike bursts occurred in synchrony with the MMCs. During fasting, gallbladder pressure, tone, and volume showed cyclic variations. During the second half of the duodenal MMC cycle, the gallbladder exhibited phasic as well as tonic contractions associated with net gallbladder emptying, whereas during the first half of the cycle the gallbladder relaxed and refilled. Minimal gallbladder volume during the MMC cycle averaged 4.8 +/- 0.7 (SE) ml compared with a maximal volume of 7.0 +/- 0.9 ml. Decreases in gallbladder volume occurred as an exponential function, whereas increases in gallbladder were linear. After feeding, the gallbladder underwent a sustained tonic contraction, without superimposed phasic contractions. Decreases in gallbladder volume occurred exponentially to a residual volume of 2.0 +/- 0.5 ml. Net postprandial gallbladder emptying was maximal by 40 min; then the volume remained unchanged for 2-3 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Radiologic amyl nitrite test for distinguishing pseudoachalasia from idiopathic achalasia.

In a simple radiologic test, amyl nitrite inhalation seems to distinguish patients with pseudoachalasia from those with idiopathic achalasia. In three pseudoachalasia patients with tumor infiltration of the distal esophagus, the narrow lower esophageal sphincter segment was unaffected by the smooth-muscle relaxant effect of amyl nitrite. In contrast, amyl nitrite caused a measurable increase of 2 mm or more in sphincter diameter in nine patients with idiopathic achalasia. The amyl nitrite test may be a useful method for distinguishing patients with pseudoachalasia from those with idiopathic achalasia.

Adult↗

Defective platelet-fibrinogen interaction in hereditary canine thrombopathia.

A unique, intrinsic, hereditary canine platelet disorder attributable to abnormal fibrinogen receptor availability is described. Thrombopathic platelets from 13 severely affected basset hounds failed to aggregate in response to all agonists tested except thrombin. Normal platelet interaction with the various stimuli was inferred on the basis of their ability to elicit unimpaired shape change in thrombopathic platelets. No quantitative differences in major platelet membrane glycoproteins, intraplatelet fibrinogen, adenine nucleotides, or serotonin uptake were detected. Dense granule secretion was impaired. The ultrastructural appearance of thrombopathic platelets was normal. Fibrinogen-platelet interaction was evaluated by reacting platelet-rich plasma (PRP) with fibrinogen coupled to polymeric acrylonitrile beads and scoring the extent of stimulus-induced agglutination. The aggregatory responses of normal and thrombopathic platelets were closely correlated with fibrinogen receptor availability. In contrast to human platelets, epinephrine-stimulated canine platelets did not interact with immobilized fibrinogen, and arachidonate generally induced only weak agglutination. Thrombopathic platelets agglutinated fibrinogen beads at reduced rates when stimulated with physiologic doses of thrombin and high-dose calcium ionophore, A23187. Our data suggest that thrombin-mediated induction of canine platelet fibrinogen receptors may proceed by pathway(s) alternate to those shared by other platelet agonists, and/or that secreted granule constituents may act synergistically with thrombin to overcome inhibition of signal-response-coupled reactions mediating the interaction of fibrinogen with its receptor. This congenital platelet defect provides further evidence, in a species other than human, for the pivotal role of fibrinogen receptor induction in platelet aggregation.

Adenine Nucleotides↗

Factor XII deficiency and von Willebrand's disease in a family of miniature poodle dogs.

The simultaneous occurrence of factor XII deficiency and von Willebrand's disease (VWD) is described in a family of Miniature Poodles affected concurrently with a familial non-spherocytic hemolytic anemia. Although there was a dominant distribution of factor XII deficiency in this family of dogs, only the dogs suffering from non-spherocytic hemolytic anemia had concurrent VWD gene expression. Neither the factor XII deficient dogs nor the VWD carrier dogs displayed bleeding tendencies.

Animals↗

Familial nonspherocytic hemolytic anemia in poodles.

Nonspherocytic hemolytic anemia, characterized by marked reticulocytosis, hepatosplenomegaly, hemosiderosis of reticuloendothelial organs and bone marrow myelofibrosis, and osteosclerosis, was diagnosed in 5 related Poodles. The unremitting anemia was clinically evident by 1 year of age, and was fatal as early as 3 years of age. Despite intense diagnostic endeavors including RBC fragility studies, RBC enzyme assays, and hemoglobin electrophoresis, the cause of this nonspherocytic hemolytic anemia remains to be determined.

Anemia, Hemolytic, Congenital↗

Prothrombin time proficiency testing: a robust grading method.

A robust two-way analysis of variance technique was applied to determine simultaneously the effects of method and thromboplastin on prothrombin time. A new approach to outlier detection for two-way analysis of variance was used. Focusing on the underlying error structure improved the uniformity of the grading procedure in the hematology proficiency testing program of the New York State Department of Health. The logarithm-transformed scale produced constancy of error variance and resulted in uniformity of the acceptable spread of data. The common variance was lower than that obtained by previous methods and allowed for a narrower acceptable range of reported prothrombin times by reducing the inflated standard deviation, thus improving the efficiency of the grading procedure. For proficiency testing, no advantage was found in the use of either a common thromboplastin or freeze-dried, coumadinized patient plasmas rather than artificially depleted commercial plasmas, except for special purposes.

Automation↗

Deficiency of the contact phase of intrinsic coagulation in a horse.

A 16-year-old gelding was examined because of weight loss, inappetence, and intermittent fever of 2 months' duration. Preliminary laboratory findings revealed anemia, hypoproteinemia, thrombocytopenia, and prolongation of the activated partial thromboplastin time. A deficiency or inhibition of coagulation factor XI, factor XII, or high molecular weight kininogen was diagnosed. This defect was not associated with a bleeding diathesis, but should be considered as a cause of prolongation of the activated partial thromboplastin time.

Animals↗

Typhlitis in adults.

Although described initially in children, typhlitis is an important clinical condition that may also occur in adults with hematologic malignancy or, less commonly, aplastic anemia. We describe 6 adult patients with typhlitis and review the salient features of this condition. In typhlitis, a necrotizing process of multifactorial origin involves the right colon alone or the right colon and other areas of the intestine as well. Secondary colonization of mucosal ulcers by colonic flora commonly leads to septicemia and pyrexia. Typhlitis may be associated with a variety of clinical and radiographic findings. However, a high index of suspicion and certain constellations of clinical and radiographic findings may lead to an accurate presumptive diagnosis of typhlitis, followed by the institution of appropriate therapy. Notwithstanding, the short-term prognosis for typhlitis remains poor.

Adolescent↗

Motilin: a mechanism incorporating the opossum lower esophageal sphincter into the migrating motor complex.

The lower esophageal sphincter (LES) exhibits cyclical phasic contractile activity synchronous with phases II and III of the gastric migrating motor complex. Motilin has been implicated in this process, although the exact mechanism is unknown. The effect of motilin on LES pressure and on gastrointestinal myoelectric activity was examined in 8 unanesthetized opossums. Intraluminal pressure was recorded by a manometric assembly incorporating a sleeve device. Myoelectric activity was recorded from the stomach, duodenum, and jejunum via implanted electrodes. The opossum LES exhibited cyclical periods of phasic contractions synchronous with phases II and III of the gastric migrating motor complex cycle. Variations in the occurrence and magnitude of the phasic LES pressure waves paralleled the spontaneous cyclic fluctuations in the level of circulating plasma motilin. Pulse doses of exogenous motilin (25-400 ng/kg) elicited a contractile LES response that mimicked the spontaneous migrating motor complex-related phasic LES contractions. This effect was dose related with the maximal response occurring at a motilin dose of 100 ng/kg. The LES response to motilin was abolished by hexamethonium and significantly antagonized by atropine and 4-diphenylacetoxy-N-methylpiperidine methiodide, but was not affected by pirenzepine, phentolamine, or naloxone. The study findings support the hypothesis that cyclic increases in circulating endogenous motilin incorporate phasic LES as well as gastric contractile activity into the gastrointestinal migrating motor complex cycle. Motilin acts on the LES by the preganglionic stimulation of cholinergic nerves.

Action Potentials↗

Multipeaked esophageal peristaltic pressure waves in patients with diabetic neuropathy.

We evaluated esophageal function in 14 consecutive insulin-dependent diabetic patients who had evidence of peripheral and autonomic neuropathy, but no esophageal symptoms. One to three contraction waves immediately followed a primary peristaltic contraction wave. The majority of these multipeaked pressure complexes consisted of two peaks. Multipeaked contractions were observed with all peristaltic waves in 12 of the 14 diabetic patients and with most of the peristaltic complexes in the remaining 2 patients. Multipeaked peristaltic waves were present in 1 of 6 diabetic patients without neuropathy, in 1 of 100 consecutive nondiabetic patients referred for suspected esophageal disease, and in 1 of 10 healthy volunteers. Double-peaked peristaltic pressure complexes in the nondiabetic control subjects differed from those present in the insulin-dependent patients by their low incidence and by a tendency to be limited to the distal esophagus. Pharmacologic responses to edrophonium and atropine suggested a possible increased cholinergic tone as the basis of the multipeaked peristaltic waves in diabetics with autonomic neuropathy.

Adolescent↗

Sleeve device functions as a Starling resistor to record sphincter pressure.

In 1976 Dent (Gastroenterology 71: 263-267) introduced a sleeve-catheter device for obtaining continuous recording of lower esophageal sphincter pressure. The infused sleeve accommodates for axial sphincter movement by providing a large surface of collapsible membrane that is capable of sensing maximal sphincter pressure at any point along the sleeve. Although sleeve performance was tested previously, the precise physical principal of its function has not been delineated. This study tests the hypothesis that the sleeve device functions as a Starling resistor. The term "Starling resistor" is an eponym that designates the physics of fluid flow through collapsible tubes. When pressure at any point along an infused collapsible conduit is greater than the intraluminal pressure at the distal end of the conduit, partial collapse occurs at some axial location along the conduit where the transmural pressure equals zero. The location of zero transmural pressure is termed the "equal pressure point" (EPP). The partial collapse at the EPP causes a local change in luminal resistance that is directly related to the magnitude of the external pressure at the EPP and accompanied by a corresponding change in the pressure upstream from the EPP. A correlate to the performance of Starling resistors is that the pressure upstream to the EPP is not affected by the downstream pressure, so long as the downstream pressure is less than the external pressure. To test our hypothesis, we evaluated sleeve performance in vitro using a two-chambered model that allowed application of static or oscillatory pressures at one or two sites along the sleeve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Variability of lower esophageal sphincter pressure in the fasted unanesthetized opossum.

The opossum has served as a useful animal model for in vivo studies of lower esophageal sphincter (LES) function. Previous investigations, however, have been confined to studies on anesthetized animals. In 10 opossums we investigated LES pressure during fasting cycles of the gastrointestinal migrating myoelectric complex (MMC) and examined the influences of anesthesia and feeding on LES pressure. Intraluminal pressure from the esophageal body, LES, and gastric antrum was recorded by a manometric assembly that incorporated a sleeve device. Myoelectric activity was recorded from the gastric antrum and duodenum via implanted electrodes. MMCs were readily recorded from all animals. MMC cycle length was 86 +/- 2.9 (SE) min. The LES exhibited cyclic changes in intraluminal pressure that occurred in synchrony with the gastric MMC cycle. During phase I of the gastric MMC cycle, LES pressure was essentially stable, although intermittent spontaneous oscillations at 3-4/min were sometimes noted. Forceful phasic LES contraction started during phase II of the gastric MMC, became maximal during phase III, and disappeared during phase I. The MMC-related phasic LES contraction occurred at a maximal rate of 1.4 +/- 0.05/min with amplitudes of 60-150 mmHg and were temporally associated with spike bursts and contractions in the gastric antrum. Pentobarbital sodium-induced anesthesia abolished MMC-related phasic LES activity and caused a transient rise in basal sphincter pressure. Phasic LES activity was also inhibited by atropine and feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗

Control mechanism of spontaneous in vitro contractions of the opossum sphincter of Oddi.

We evaluated the control mechanism of peristaltic contractions in the opossum sphincter of Oddi (SO) by means of an in vitro preparation. At each of four sites spaced uniformly along the sphincter segment, a force transducer recorded contractions while a monopolar electrode recorded myoelectric activity. Spontaneous myoelectric and contractile activity occurred in 15 of the 20 intact SO specimens studied. Electrical recordings showed characteristic control waves and response activity. Each control wave was invariably accompanied by a phasic contraction, irrespective of whether or not response activity was superimposed on the control wave. The predominant motor activity of the SO was antegrade peristalsis. Retrograde peristalsis occurred when antegrade peristalsis failed to traverse the entire sphincter. Spontaneous SO phasic contractions were not antagonized by tetrodotoxin. Muscle rings sectioned from the SO exhibited spontaneous phasic contractions with a proximal-to-distal gradient of intrinsic contraction frequencies. We conclude that a) the frequency of SO phasic contractions is determined by control wave frequency, b) spontaneous SO peristalsis is myogenic in origin and may be modeled by a linear array of bidirectionally coupled relaxation oscillators, c) the predominance of antegrade peristalsis may be explained by a high-frequency oscillator in the proximal SO that drives the slower, more distal oscillators, d) retrograde peristalsis is initiated by an ectopic oscillator in the distal SO when antegrade contractions fail to propagate the entire length of the SO, and e) ectopic SO contractions can propagate retrograde when the more proximal oscillators are not in their absolutely refractory state.

Ampulla of Vater↗

Megakaryocytic infection and thrombocytopenia in African swine fever.

Pigs infected with an African swine fever field isolate of modified virulence became acutely thrombocytopenic four to five days after the onset of fever and viremia. By eight days after inoculation, all pigs were thrombocytopenic. Immunofluorescence microscopy demonstrated that 2 to 10% of the megakaryocytes were infected. By 13 days after inoculation, platelet counts returned to within normal limits, and there was megakaryocytic hyperplasia despite a continued viremia. Secondary complications delayed the return of normal circulating platelet levels in some pigs. The clinical findings of African swine fever are discussed in light of the gross and histologic lesions.

African Swine Fever↗