Biomedical subjects

S M Collins

Publications and source records attributed to S M Collins.

At least 127 records · Page 7Linked to original sources

PubMed1992

Impaired acetylcholine release in the inflamed rat intestine is T cell independent.

We investigated mechanisms underlying the suppression of [3H]acetylcholine ([3H]ACh) release from myenteric plexus-longitudinal muscle preparations of rats infected 6 days previously with Trichinella spiralis. There was a 73% suppression of KCl-evoked release of [3H]ACh in the jejunum, and a 76% suppression was observed in the worm-free ileum, indicating that the local presence of the parasite in the lumen is not prerequisite for the suppression of ACh release from the myenteric plexus. Treatment of rats with betamethasone (3 mg.kg-1.day-1 ip) during the infection prevented the acute inflammatory response and attenuated the suppression of [3H]-ACh release (from 73 to 22%) in the jejunum of infected rats. This finding is consistent with the hypothesis that the suppression of ACh release occurs as a result of the inflammatory process. Marked suppression of [3H]ACh release was also seen in T. spiralis-infected nude athymic rats, which were shown to lack functioning T lymphocytes. Thus changes in ACh release are not dependent on T lymphocytes. Taken in conjunction with our previously published study showing that altered muscle function in this model is T cell dependent, the results of the present study indicate that different components of the inflammatory response mediate changes in smooth muscle and myenteric nerves in the T.spiralis infected rat.

Acetylcholine↗

PubMed1992

Is the irritable gut an inflamed gut?

Recent advances in the field of neuroimmunology have provided clear demonstrations of i) the neuromodulation of immune function, and ii) the involvement of the immune system in responses induced by psychologic stress in animals and in man. This has led to speculation about the role of the immune system in psychosocial disease. The irritable bowel syndrome (IBS) is characterized by chronic gastrointestinal dysfunction, which may reflect in altered motility, epithelial function, or sensory perception in the gut. IBS is heterogeneous not only in terms of its clinical presentation but also in terms of its pathogenesis, and factors ranging from psychoneurotic behavior and emotional stress, to dietary fiber deficiency, food intolerance, and enteric infection have been implicated. There is evidence of an increase in the inflammatory cells present in the gut of some IBS patients and in an emerging literature that demonstrates the immunomodulation of the motor system of the gut. These findings invite speculation that the immune system may play a role in the pathogenesis and pathophysiology of at least a subpopulation of IBS patients.

Colonic Diseases, Functional↗

PubMed1991

Factors related to the presentation of patients with thick primary melanomas.

OBJECTIVE: To identify any characteristics of patients that are associated with presentation with thick primary melanoma. DESIGN: This was a retrospective survey of the clinical records of 1300 patients attending the Newcastle Melanoma Unit. Characteristics of 131 patients with thick melanomas (defined as 3 mm or greater in thickness) were compared with those of 543 patients with thin melanomas (defined as 0.75 mm or less in thickness). Comparisons were made using contingency table analysis, Wilcoxon rank sum tests, log rank analysis and logistic regression. SETTING: The Newcastle Melanoma Unit is a tertiary referral centre for the treatment of primary melanoma. PATIENTS: We surveyed all 1300 patients attending the Newcastle Melanoma Unit over the years 1981-1990. They represented approximately 90% of the patients in the Hunter region of New South Wales who developed melanoma during this period. Excluded from analysis were 39 patients with occult primary melanomas, 79 with multiple primary melanomas, 51 with primary melanomas of unknown thickness and seven with incomplete records, leaving 1124 patients in the study. MAIN OUTCOME MEASURES: These were selected before the results were known. The hypothesis was generated following analysis of the data. RESULTS: Patients with thick primary melanoma were more likely to be men (68% men and 32% women in the thick melanoma group, compared with 45% and 55% respectively in the thin melanoma group, P less than 0.005) over 60 (75% were over 50 years of age in the thick group versus 33% in the thin melanoma group, P less than 0.001) with nodular melanoma (62%, versus 2% in the thin melanoma group, P less than 0.001) and with melanoma on the head and neck (27%, versus 12% in patients with thin melanoma, P less than 0.005). The time from detection of a change in skin to diagnosis was not longer for those with thick compared to those with thin melanomas. CONCLUSION: The greatest problem of those with thin melanomas. CONCLUSION: The greatest problem of detecting melanoma at an early (surgically curable) stage appears to be in patients over the age of 50 who have nodular melanoma, particularly in the head and neck.

Adolescent↗

PubMed1991

Impaired sympathetic nerve function in the inflamed rat intestine.

The effect of intestinal inflammation on norepinephrine release from the myenteric plexus in the Trichinella spiralis-infected rat was assessed. Longitudinal muscle-myenteric plexus preparations were preincubated with [3H]norepinephrine and release was evoked by electrical field stimulation and KCl administration. Preincubation of preparations with desipramine or pretreatment of rats with 6-hydroxydopamine significantly suppressed the uptake and evoked release of [3H]norepinephrine; electrical field stimulation but not KCl-evoked release of [3H] norepinephrine was sensitive to tetrodotoxin. These results confirm the presence of functioning sympathetic nerves in the preparations. T. spiralis infection was associated with significant suppression of both electrical field stimulation and KCl-evoked release of [3H]norepinephrine on the sixth day postinfection, and the suppression persisted 100 days postinfection. No suppression of [3H]norepinephrine release was seen in the worm-free and noninflamed ileum of infected rats. Suppression of [3H]norepinephrine release from the jejunum of infected rats was attenuated by treatment with betamethasone (3.0 mg/kg SC daily). These results are consistent with the hypothesis that intestinal inflammation suppresses the release of norepinephrine from the myenteric plexus in the Trichinella-infected rat.

Animals↗

PubMed1991

T-lymphocyte modulation of intestinal muscle function in the Trichinella-infected rat.

Jejunal longitudinal muscle from Trichinella-infected Sprague-Dawley rats generates increased tension in vitro 6 days after infection. To investigate the extent to which this increase is dependent on T lymphocytes, smooth muscle contraction was examined in athymic rats (rnu/rnu) and in their euthymic (rnu/+) littermates 6 days after infection. In both thymus-bearing and athymic rats, the highest concentrations of Trichinella were found in the jejunum where mucosal myeloperoxidase activity was increased. Muscle from infected euthymic rats generated more tension to carbachol or 5-hydroxytryptamine than that of noninfected controls. In contrast, there was no difference between the responses of muscle from infected and control athymic animals. However, when athymic rats were reconstituted with splenic mononuclear cells, increased tension to carbachol or 5-hydroxytryptamine was observed after infection. T-lymphocyte activity was demonstrated by in vitro assays in euthymic or reconstituted rats but not in athymic rats. It is concluded that some changes in intestinal smooth muscle function following Trichinella spiralis infection in the rat are T lymphocyte dependent. These results support the concept of immunomodulation of intestinal smooth muscle function.

Analysis of Variance↗

PubMed1991

Airway responsiveness to inhaled methacholine in patients with irritable bowel syndrome.

We examined whether patients with irritable bowel syndrome have increased airway responsiveness by measuring forced expiratory volumes in 1 second (FEV1) after inhalation of increasing concentrations of methacholine. Responses obtained in 11 IBS patients were compared with those obtained in 11 normal subjects and in 11 subjects with organic disease of the gut or its related organs. All subjects were selected so that other factors that might contribute to increased airway responsiveness were excluded. The methacholine concentration that caused a 20% fall in the FEV1 (PC20), as well as the reduction in FEV1 induced by each methacholine concentration, were used to assess airway responsiveness. The geometric mean PC20 was 197.6 mg/mL (%SEM, 1.15) for normal subjects, 83.9 mg/mL (%SEM, 1.51) for subjects with organic bowel disease (P = 0.012), and only 12.8 mg/mL (%SEM, 1.74) for IBS patients (P less than 0.0001). The 22.5% +/- 2.5% decrease in FEV1 induced by 64 mg/mL of methacholine in IBS patients was significantly greater than that of 12.3% +/- 1.5% observed in healthy subjects (P = 0.003). In contrast, the 15.7% +/- 2.0% decrease in FEV1 observed in patients with organic disease was not different from that seen in normal subjects (P = 0.189). We conclude that IBS is associated with increased airway responsiveness following challenge with methacholine.

Administration, Inhalation↗

PubMed1991

Correlations between cardiac imaging and electrophysiological studies: what is the state of the art?

Changes in ventricular activation produced by bundle branch block, pre-excitation, and ventricular tachycardia and pacing have been studied by various cardiac imaging modalities. We reviewed results of previously published and newly generated imaging data correlated with known or measured electrophysiological studies. Echocardiography has been demonstrated to grossly correlate with abnormal ventricular wall motion when activation sequence was altered. However, phase analysis of radionuclide and cine-computed tomography have provided detailed noninvasive activation data that correlated reasonably well with measured electrical activation sequence in both animals and man. Analysis of wall motion may not predict activation sequence when muscle is damaged or excessive translational movement of the heart occurs. Body surface mapping of electrical potentials has the capability to accurately but noninvasively register an electrical activation image of the heart that circumvents the problems of imaging contraction sequence. In the future, body surface potential mapping should be more widely used clinically and experimentally.

Animals↗

PubMed1990

The effect of naloxone on lipid-induced pyloric motor response in humans.

This study examines whether opioid receptors are involved in the mediation of the pyloric motor response to intraduodenal lipid infusion. Antral, pyloric, and duodenal manometry was performed in seven healthy volunteers with a sleeve/multiple side-hole manometric assembly. Triglyceride emulsion and normal saline were infused alternately into the duodenum through the manometric assembly for two 30-minute periods each. Naloxone was then administered as an IV bolus, 40 micrograms/kg, followed by an infusion of 60 micrograms.kg-1.h-1 that was continued during testing of the duodenal infusates. Before naloxone administration, intraduodenal lipid produced significant increases in the rate of isolated pyloric pressure waves and basal pyloric tone when compared with saline (P = 0.009 and 0.027, respectively). The pyloric motor responses were unchanged after administration of naloxone, indicating that in humans, naloxone-sensitive opioid mechanisms are not involved in the mediation of lipid-induced pyloric motor responses.

Adult↗

PubMed1990

Effect of dietary fiber on symptoms and rectosigmoid motility in patients with irritable bowel syndrome. A controlled, crossover study.

The aims of this study were to determine (a) whether dietary fiber supplements modify symptoms in patients with irritable bowel syndrome, (b) the effect of fiber on rectosigmoid pressures, and (c) the relationship, if any, between rectosigmoid pressure and symptoms. Fourteen patients entered and 9 completed a double-blind, controlled, cross-over study of 7 mo duration. The mean age was 26 yr (range, 18-37). Patients received 4 cookies daily containing 20 mg corn fiber or placebo. Symptoms and compliance were evaluated monthly. Rectosigmoid pressures and dietary intake were evaluated at the outset and completion of each study arm. Symptoms improved during both fiber and placebo treatments. Those symptoms demonstrating significant improvement with time were pain severity, stool frequency, stool consistency (p = 0.001), number of additional gastrointestinal symptoms present (p = 0.02), and total symptom score (p less than 0.001). Rectosigmoid pressures were not significantly altered by fiber or placebo. Fasting pressures at the distal recording site tended to correlate with pain severity (r = 0.6; p = 0.06). It was concluded that (a) corn fiber and placebo were both effective in alleviating symptoms, (b) there was a correlation between symptom severity and fasting rectosigmoid pressure, and (c) there was a trend toward reduction in fasting and postprandial rectosigmoid pressures after fiber therapy.

Adult↗

PubMed1990

Tissue characterization of chronic myocardial infarction.

Determination of magnetic resonance (MR) relaxation times (T1 and T2) and ultrasound backscatter are potential methods of noninvasive myocardial tissue characterization. The authors postulated that infarct-related collagen deposition in a canine chronic myocardial infarction model would alter T1 and T2 relaxation times. Further, we sought to compare the changes in T1 and T2 with backscatter measurements. Eight animals were studied 4 to 6 weeks after occlusion of the left anterior descending coronary artery; standard echocardiography showed each to have left ventricular wall motion abnormalities. Time-averaged backscatter and cyclic backscatter variation (at 5 MHz) were measured in the open-chest animal with corresponding normal and infarcted areas undergoing in vitro T1 and T2 measurements (at 20 MHz) and water and hydroxyproline concentration analysis. Significant increases in T2, time-averaged ultrasound backscatter, and hydroxyproline concentration were found in the infarcted myocardium compared with normal muscle. Cyclic variation in backscatter and water content were not significantly different between the two groups. Although backscatter, T2, and tissue collagen content increased in the infarcted myocardium, a significant relationship was not found among these variables.

Animals↗

PubMed1990

Altered smooth muscle function in worm-free gut regions of Trichinella-infected rats.

We have extended a recent study demonstrating increased contractility of jejunal smooth muscle of rats infected with the nematode parasite Trichinella spiralis, the primary habitat of which is the jejunum. In this study, muscle from the worm-free ileum of infected rats showed decreased contractility compared with control, illustrating regional differences in muscle responses to the infection. However, in jejunal muscle from worm-free segments that had been excluded from the rest of the gut before the infection, we observed increased tension generation, suggesting a systemic mechanism. To evaluate whether the changes in jejunal muscle were due to the host's inflammatory reaction, the effect of beta-methasone was examined. In a dose of 3.0 mg/kg sc daily, the steroid abolished the increase in myeloperoxidase activity associated with the infection and attenuated the increased tension generation in jejunal muscle from Trichinella-infected rats. These results support the hypothesis that alterations in intestinal smooth muscle function in this model do not require the presence of the parasite in the lumen and are mediated by the host's inflammatory reaction.

Animals↗

PubMed1990

Characterization of acute experimental left ventricular thrombi with quantitative backscatter imaging.

Two-dimensional echocardiography is an excellent technique for detecting left ventricular thrombi, however, acute clot is sometimes difficult to differentiate from adjacent myocardium and intracavitary signals. We hypothesized that quantitative assessment of the acoustic properties of acute left ventricular thrombi using a quantitative backscatter imaging system would permit the differentiation of thrombus from adjacent myocardium and intracavitary echoes. Acute, experimental left ventricular thrombi in seven dogs were evaluated with a quantitative backscatter imaging system that allowed the measurement of relative integrated backscatter and cyclic (i.e., diastolic minus systolic) variation in integrated backscatter. Coronary ligation abolished the cyclic variation in relative backscatter that occurred in normal myocardium. The end-diastolic relative backscatter in the thrombus (16.9 +/- 1.3 dB) was significantly higher than in apical myocardium (13.2 +/- 0.6 dB, p less than 0.05). There was no significant difference in the cyclic variation in relative backscatter among thrombus, ischemic myocardium, or intracavitary blood. Thus, the quantitative assessment of the acoustic properties of left ventricular thrombi can be useful in their detection and in the differentiation from myocardium and intracavitary signals.

Animals↗

PubMed1989

Feasibility of identifying amyloid and hypertrophic cardiomyopathy with the use of computerized quantitative texture analysis of clinical echocardiographic data.

Ultrasound tissue characterization, the evaluation of certain physical properties of a tissue based on its acoustic properties, is an evolving application in echocardiography. The ability to identify acutely and chronically injured tissue has been demonstrated in a number of animal studies, but data in humans are limited. The present study tested the hypothesis that quantitative echocardiographic texture analysis, a method of evaluating the spatial pattern of echoes in echocardiographic images, would differentiate amyloid and hypertrophic cardiomyopathy from normal myocardium. Routine clinical echocardiographic data were obtained on 34 subjects at the Mayo Clinic (10 normal subjects, 10 patients with amyloid heart disease, 8 patients with hypertrophic cardiomyopathy and 6 patients with left ventricular hypertrophy due to hypertension). Standard videotape recordings of these echocardiograms were analyzed at the University of Iowa. Echocardiographic data were digitized with use of a calibrated, 256 gray level digitization system. Quantitative texture analysis was performed on data from the ventricular septum and posterior left ventricular wall in end-diastolic and end-systolic, short-axis and long-axis echocardiographic images. The gray level run length texture variables were able to discriminate hypertrophic cardiomyopathy and amyloid heart disease from normal myocardium and from each other (p less than 0.0083 for comparisons of the quantitative texture features of amyloid versus hypertrophic cardiomyopathy versus normal by multivariate analysis of variance). The texture of the myocardium in hypertensive left ventricular hypertrophy not associated with amyloid or hypertrophic cardiomyopathy was in general not significantly different from that of normal myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Upper esophageal sphincter tone and reactivity to stress in patients with a history of globus sensation.

Anxiety and abnormal upper esophageal sphincter function have been ascribed ill-defined roles in the etiology of globus sensation. In this study, we examined the psychological profile and effect of acute mental stress (dichotic listening task) on UES tone in seven patients reporting to the clinic with globus sensation and 13 healthy controls. Alterations in heart rate, blood pressure, frontalis EMG, and skin conductance confirmed the effectiveness of the stress test in patients and controls. During resting conditions, UES pressure (mean +/- SE) in patients (40.4 +/- 4.6 mm Hg) did not differ significantly from controls (46.5 +/- 4.7 mm Hg). In response to stress, UES pressure rose by 31% in patients (P = 0.04) and by 25% in controls (P = 0.002). The stress-induced rise in UES pressure in patients (9.5 +/- 3.8 mm Hg) was not significantly different to that observed in controls (11.8 +/- 3.0 mm Hg). Psychological profiles of globus patients presenting to the clinic revealed them to be more introverted, anxious, neurotic, and depressed than normal controls. We conclude that in patients with a history of globus sensation, resting UES pressure and its response to stress is normal. Although individuals presenting to the clinic with globus sensation showed increased levels of psychoneurosis, acute, predictable stress is not a factor in the genesis of globus sensation. UES hyperresponsiveness to other stimuli or subjective intolerance to changes in UES pressure could account for symptoms of globus sensation.

Adult↗

PubMed1989

Pyloroplasty does not disrupt liquid phase gastric emptying or CCK-induced satiety.

To assess the hypothesis that cholecystokinin (CCK) induces satiety by constricting the pylorus and inhibiting the rate of gastric emptying, we impaired pyloric function in 8 experimental animals using a Heincke-Mikulicz pyloroplasty procedure. Liquid phase gastric emptying was measured with a double-sampling procedure. We found that pyloroplasty did not disrupt the pattern of gastric emptying of saline or nutrient under control conditions. CCK also showed emptying in both pyloroplasty and control animals. Finally, pyloroplasty did not affect the ability of CCK to induce satiety. We provide functional and morphological evidence that the pyloroplasty procedure successfully impaired constriction of the pyloric sphincter. These findings suggest that the pylorus is not critical to the control of liquid phase emptying and, together with the absence of a pyloroplasty effect on CCK-induced satiety, seriously question the adequacy of the pyloric mediation hypothesis.

Animals↗

PubMed1989

Altered smooth muscle contraction and sodium pump activity in the inflamed rat intestine.

We examined changes in membrane function underlying the increased contractility of jejunal longitudinal muscle to carbachol in rats infected 6 days previously with Trichinella spiralis. Muscarinic receptor characteristics were examined in particulate fractions using [N-methyl-3H]scopolamine (NMS). There was a significant reduction in the total number of binding sites on muscle from infected rats, but the affinity for NMS was unchanged. Similarly, in competition studies, the binding of carbachol to high or low affinity sites was not significantly different in tissue from control or infected rats. However, we observed an 89% suppression of the activity of K+ -stimulated ouabain-sensitive p-nitrophenylphosphatase (pNPPase), an enzyme marker for the Na+ -K+ pump, in plasma membranes from infected compared with control rats. Similar results were obtained in 86Rb uptake studies. In contractility studies, evidence for the electrogenicity of the Na+ -K+ pump was obtained by demonstrating that pump activation by K+, Rb+, or Cs+ was associated with tissue relaxation with a rank order of potency that was identical to that for stimulation of pNPPase activity by these ions. Conversely, pump inhibition by vanadate increased tone and abolished phasic contractions in muscle from control or infected rats. This was accompanied by an increased response to carbachol in muscle from control but not infected rats. In addition, pump inhibition by removing extracellular K increased tone in control tissue but decreased tone in muscle from T. spiralis-infected rats, presumably because of preexisting pump suppression. These results are consistent with the hypothesis that suppression of electrogenic Na-pump activity contributes to the increased contractility of jejunal muscle in rats infected with T. spiralis.

Animals↗

PubMed1989

Impaired acetylcholine release from the myenteric plexus of Trichinella-infected rats.

We examined the release of acetylcholine (ACh) from jejunal longitudinal muscle-myenteric plexus preparations in noninfected control rats and in rats infected 6, 23, or 40 days previously with Trichinella spiralis. ACh release was assessed by preincubating the tissue with [3H]choline and measuring the evoked release of tritium. The uptake of 3H was significantly less in tissue from T. spiralis-infected rats compared with control. In tissues from either infected or control animals, electrical field stimulation (30 V, 0.5 ms, 10 Hz for 1 min), or veratridine (6-30 microM) induced 3H release that was tetrodotoxin sensitive. Depolarization by KCl (25-75 mM) also caused 3H release, but this was only partially reduced by tetrodotoxin. Radiochromatographic analysis indicated evoked release of 3H to be almost entirely [3H]ACh. In rats infected 6 days previously with T. spiralis, [3H]ACh release induced by KCl, veratridine, and field stimulation were decreased at least 80%. The suppression of [3H]ACh release induced by veratridine or KCl was fully reversible after 40 days postinfection, but field-stimulated responses remained approximately 50% of control values. These results indicate that T. spiralis infection in the rat is accompanied by a reversible suppression of ACh release from the longitudinal muscle-myenteric plexus of the jejunum.

Acetylcholine↗

PubMed1989

Gastric emptying changes are neither necessary nor sufficient for CCK-induced satiety.

If gastric emptying plays a significant role in the satiety produced by exogenous cholecystokinin octapeptide (CCK-8) then 1) the effects on emptying and feeding should share similar kinetics and 2) peptides that inhibit emptying should also inhibit feeding. In the first experiment, CCK-8 (5.6 micrograms/kg) injected immediately before the introduction of an intragastric load (10 ml saline) or presentation of a test meal (15% sucrose) produced a rapid inhibition of both emptying and feeding. In contrast, the same dose administered 15 min before testing caused no inhibition of emptying, even though it retained the ability to reduce meal size. In experiment 2, the abilities of the peptides pentagastrin (100 micrograms/kg), bombesin (8 and 16 micrograms/kg), and secretin (2.86, 14.3, and 28.6 micrograms/kg) to reduce food intake and inhibit emptying were tested. Pentagastrin influenced neither food intake nor gastric emptying. Bombesin caused a small transient delay in emptying but a large and sustained eating suppression. However, a high dose of secretin caused no significant reduction of food intake, in spite of the fact that it inhibited emptying to the same degree as 1.4 micrograms/kg CCK-8, which does reduce intake. These results suggest that the inhibition of emptying by CCK is not sufficient to explain the satiety effect of CCK-8.

Animals↗