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Biomedical subjects

S M Collins

Publications and source records attributed to S M Collins.

At least 19 recordsLinked to original sources

Variable morphology of coronary atherosclerosis: characterization of atherosclerotic plaque and residual arterial lumen size and shape by epicardial echocardiography.

The purpose of this study was to evaluate the in vivo characteristics of coronary atherosclerosis by using high frequency epicardial echocardiography. High frequency epicardial echocardiography was used to evaluate residual lumen and wall morphology at the sites of maximal coronary atherosclerosis in 26 patients undergoing coronary artery bypass grafting. The maximal/minimal wall thickness ratio was 3.1 +/- 0.2 (mean +/- SEM) with a large range (1.3 to 7.5). Portions of the wall were normal in 16 of 31 lesions; the percent normal circumference ranged from 9% to 85%. Maximal/minimal lumen diameter ratio was 1.5 +/- 0.1 (range 1.1 to 2.9). The shape of the residual coronary lumen was noncircular in 16 lesions: oval in 13 and complex in 3. The residual coronary lumen was eccentrically placed within six arteries. These data emphasize the variability of residual lumen and wall geometry in atherosclerosis.

Coronary Artery Bypass

Increased levels of substance P in the myenteric plexus of Trichinella-infected rats.

Changes in immunoreactive substance P concentrations were investigated in longitudinal muscle-myenteric plexus preparations from the inflamed jejunum of Trichinella spiralis-infected rats. The substance P concentration increased within 2 days of infection and increased fivefold by day 6; in contrast, there was no significant increase in substance P in the noninflamed ileum. In vitro exposure of preparations from infected rats to scorpion venom reduced substance P levels by 88%. In addition, no increase in substance P was observed in rats that had been treated with capsaicin as neonates or as adults before infection. Treatment of infected rats with betamethasone attenuated the inflammatory response to the infection and prevented the increase in substance P. Furthermore, no significant increase in substance P concentration was seen in congenitally athymic rats infected with T. spiralis. This study is consistent with the hypothesis that inflammation increases substance P in myenteric nerves by a process that involves T lymphocytes.

Animals

Effect of inflammation of enteric nerves. Cytokine-induced changes in neurotransmitter content and release.

The results of our previously published work provide evidence of inflammation-induced functional disturbances in the enteric nervous system. Data presented in this paper describe our preliminary results indicating that the altered function in enteric nerves in the nematode-infected rat model of intestinal inflammation is mediated by interleukin-1. This is based on the ability of the exogenous cytokine to mimic changes observed in the model, and on the ability of a specific IL-1 antagonist to attenuate these changes. In addition, we have identified mechanisms underlying the actions of IL-1 in the myenteric plexus. Our data are consistent with a direct interaction between the cytokine and neural membranes. In addition, the delayed effect of IL-1 beta on neurotransmitter release appears to be due to the release of endogenous IL-1, most likely from macrophage-like cells in the myenteric plexus (Fig. 3). If such cells possess receptors for neuropeptides, as has been found with macrophages elsewhere in the gut, a neuroimmune axis would exist in the myenteric plexus. Thus, the finding of a source of IL-1 in the plexus of the noninflamed intestine invites speculation on a neuromodulatory role of the cytokine within the enteric nervous system.

Animals

Inflammation causes hyperplasia and hypertrophy in smooth muscle of rat small intestine.

Inflammation of the rat jejunum with Trichinella spiralis causes altered smooth muscle contractility by day 6 postinfection (PI). We investigated the association of structural change in the smooth muscle layers with inflammation. By day 6 PI, smooth muscle area in cross sections of jejunum increased (P less than 0.05) in longitudinal (LM) and circular (CM) muscle layers. Nuclei counting in cross sections showed that cell number increased two- to threefold in CM and LM, and this increase was not reversed on day 23 PI. Estimation of cell size showed significant hypertrophy by day 6 PI in both muscle layers. [3H]thymidine autoradiography showed that the labeling index (LI) of jejunal LM and CM increased sharply on day 4 PI and peaked on day 6 PI (10- to 15-fold increase). The noninflamed ileum showed a smaller trophic response, with no significant change in area or nuclei number, the LI was increased only on day 6 PI in the ileal CM and was unchanged in LM. Thus extensive hyperplasia and hypertrophy of smooth muscle cells are associated with intestinal inflammation.

Animals

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

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

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

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

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

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

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

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

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

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

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

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

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

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