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Biomedical subjects

M J Murray

Publications and source records attributed to M J Murray.

At least 145 records · Page 8Linked to original sources

Endoscopic appearance of gastric lesions in foals: 94 cases (1987-1988).

Of 183 foals examined by use of gastroendoscopy during 1987 and 1988, 94 had gastric lesions. Sixty-eight of 120 foals in the 1- to 85-day-old age range had endoscopically confirmed gastric lesions, and 26 of 63 foals in the 90- to 310-day-old age range had gastric lesions. Lesions were observed most frequently in the stratified squamous mucosal epithelium, particularly adjacent to the margo plicatus. Lesions were observed in the gastric glandular mucosa in 26 of the 94 foals with gastric lesions, and with a greater frequency in foals with a clinical disorder than in foals with no disorder (27% vs 3%). In young foals, lesions were consistently observed in the stratified squamous mucosal epithelium adjacent to the margo plicatus along the greater curvature of the stomach at 2 specific sites. These lesions were frequently associated with desquamation of the stratified squamous mucosal epithelium, which was observed in 69 of the 82 foals less than or equal to 30 days old and in 13 of the 101 foals greater than 30 days old. Lesions in the stratified squamous mucosal epithelium adjacent to the margo plicatus were associated with concurrent clinical disorders in foals greater than 90 days old, but developed with identical frequency in foals less than 90 days old with or without a clinical disorder. Lesions in the stratified squamous mucosal epithelium along the lesser curvature of the stomach were observed only in foals with concurrent clinical disorder, and with a higher frequency in foals greater than 90 days old than in younger foals (24% vs 3%).

Animals↗

Two different subunits associate to create isoform-specific platelet-derived growth factor receptors.

Recent evidence has demonstrated that there is more than one form of platelet-derived growth factor (PDGF) receptor and that these receptors differ in their specificity for the multiple isoforms of PDGF. We present evidence that high affinity binding of PDGF requires association of two different receptor subunits: an alpha-subunit that can bind either a B- or an A-chain of PDGF, and a beta-subunit that can bind only a B-chain. The alpha- and beta-subunits appear to be similar in size but can be distinguished by binding specificity and by an antireceptor monoclonal antibody, PR7212, which recognizes only the beta-subunit. In the absence of PDGF, these subunits either exist separately or form rapidly reversible complexes. In the presence of PDGF, receptor subunits of appropriate specificity interact with a PDGF molecule to form a high affinity complex. Both the absolute and relative numbers of these two PDGF receptor subunits vary on different cell types and correspond to differences in the mitogenic sensitivity of cells to the different PDGF isoforms.

Adult↗

Topical growth factors and wound contraction in the rat: Part I. Literature review and definition of the rat model.

The isolation and production of growth factors and the observation that a platelet extract will promote wound healing in chronic wounds has led to an interest in the study of growth factors and wound healing. We wished to study the effect of platelet-derived growth factor on wound contraction. However, because studies of growth factors and wound contraction are quite recent, we could find only two models described in the literature and neither seemed ideal. Both used small wounds, which are difficult to measure, anesthetics with slow induction and recovery and which are difficult to titrate, and no dressings, which permits the animals to lick the wounds and possibly introduce other growth factors. We therefore reviewed wound contraction models used for other studies. In particular, we reviewed the animal used, anesthetic, wound size and shape, dressing methods, scab treatment, and measurement and comparison techniques. We then combined features of many of them into a model that solves the problems listed and permits the study of topically applied growth factors and wound contraction. The composite model to be described uses a large, circular wound on the rat, halothane anesthesia, and flexible, Tubigrip dressings.

Administration, Topical↗

Topical growth factors and wound contraction in the rat: Part II. Platelet-derived growth factor and wound contraction in normal and steroid-impaired rats.

The wound contraction model described in Part I was used to study topically applied, recombinant platelet-derived growth factor (rPDGF-BB) and wound contraction in normal and steroid-impaired rats. Circular wounds 4 cm in size were made on the dorsum of the rats with halothane anesthesia. Five groups of 20 normal rats each were treated with the vehicle alone and four concentrations of rPDGF-BB (0.5, 1.0, 3.0, and 10.0 micrograms/ml). Four groups of 20 steroid-impaired rats each were treated with the vehicle alone and three concentrations of rPDGF-BB (0.5, 1.0, and 3.0 micrograms/ml). The wounds were dressed with 2 x 2 gauze, Adaptic, 4 x 4 gauze, and Tubigrip. The investigators were blinded to the treatments until the completion of the experiment, and the treatments were applied in random order. Dressings were changed every 2 to 3 days for 14 days and the wound areas were determined, expressed as a fraction of the original, and plotted versus time. The areas under the curves and the means of the fraction open each day were compared between groups using Student's t-test. The treatment with 3.0-micrograms/ml rPDGF-BB accelerated the rate of wound contraction in the steroid-impaired animals (p less than 0.05).

Administration, Topical↗

Gastric ulcers in horses: a comparison of endoscopic findings in horses with and without clinical signs.

Gastroendoscopic examinations were performed on 187 horses, ranging from one to 24 years. Eighty-seven horses had clinical problems including chronic, recurrent colic for seven or more days (25), one or more episodes of colic within the previous seven days (13), or acute colic (10), diminished appetite (53), poor bodily condition (40), and/or chronic diarrhoea (9). One hundred horses that had no signs of gastrointestinal problems were examined as part of a gastroendoscopic survey. Lesions observed in the squamous fundus, squamous mucosa adjacent to the margo plicatus along the greater curvature, glandular fundus, and the squamous mucosa along the lesser curvature were scored on a scale of 0-4, with 0 representing no lesions and 4 representing the most severe lesions. The mean endoscopic scores for the squamous fundus, margo plicatus and lesser curvature were significantly greater (P < 0.001) in horses with clinical signs than those without signs. This was because of the greater number of horses with lesions in the symptomatic group (80/87) compared to those without signs (52/100), and the greater severity of lesions in the horses with clinical signs. Of the horses, 74 were in race training. There was a significantly (P < 0.01) greater prevalence and severity of lesions at all sites except the glandular fundus in horses in training compared to those not in training, and in the horses in training with clinical signs (n = 37) compared to those in training without clinical signs (n = 37).

Animals↗

Regional gastric pH measurement in horses and foals.

The pH of the gastric mucosal surface and gastric content was measured in 18 foals (mean age: 20 days) and 27 horses (mean age: 2.9 years) with a pH electrode passed through an endoscope biopsy channel. A reference electrode was attached to a shaved area on the neck. pH Measurements of the gastric mucosal surface at the dorsal squamous fundus (SF), squamous mucosa adjacent to the margo plicatus (MP), glandular fundus (GF) and the fluid or feed contents of the stomach were recorded in duplicate for each animal. In adult horses, the SF pH was greatest (5.46 +/- 1.82), with a decreasing pH ventrally toward the MP (4.12 +/- 1.62), to the glandular fundic mucosa (3.09 +/- 1.90), and fluid contents (2.72 +/- 1.86). The differences in pH at each site within the stomach were significant (P < 0.05). In foals, mean pH measurement of the SF was 4.88 +/- 1.30, the MP was 4.92 +/- 1.29, the GF was 2.10 +/- 1.45, milk and fluid contents was 1.85 +/- 0.53 (six foals), and feed contents was 3.39 +/- 1.77 (12 foals). The pH of the SF and MP were significantly greater (P < 0.05) than that of feed contents, which was significantly greater (P < 0.05) than that of the glandular mucosal surface and fluid contents. The results indicate a dorsal to ventral pH gradient of the gastric mucosal surface in adult horses, and that gastric acid secretion is competent in young foals.

Aging↗

Treatment of gastric ulcers in horses with histamine type 2 receptor antagonists.

Of 55 horses treated with histamine type 2 (H2) receptor antagonists for gastric ulcers, 32 were examined by gastroendoscopy before and after treatment. Distribution and severity of lesions in the squamous fundus (sf), margo plicatus (mp), glandular fundus (gf), lesser curvature (lc) and cardia (car) were recorded. Severity of the lesions was scored 0-4 (0 = no lesions, 4 = most severe). On initial examination, lesions were most frequently observed at the mp (28/32) and least frequently observed in the gf (5/32). There was endoscopic confirmation of improvement in lesion scores in each region, although the magnitude of improvement and duration of treatment required to affect total healing varied by region. The mean (+/-sd) changes in lesion scores in each region of the stomach after treatment were: -1.92 +/- 1.43 (sf), -2.27 +/- 0.98 (mp), -1.60 +/- 0.80 (gf), -1.20 +/- 1.81 (lc), and -2.00 +/- 1.85 (car). Clinical improvement was noted in 54 of 55 animals, as indicated by decreased frequency of colic episodes, weight gains, and improved appetite. It was concluded that H2 antagonists are an effective treatment of gastric ulcers in horses, as determined by endoscopic and clinical improvement.

Animals↗

Platelet isoforms of platelet-derived growth factor stimulate fibroblasts to contract collagen matrices.

Fibroplasia and angiogenesis are essential components of tissue repair when substantial tissue has been lost at a site of injury. Platelets and monocyte/macrophages accumulate at these sites and release a variety of growth factors that are thought to initiate and sustain the repair. Often the involved tissue contracts, a process that can markedly reduce the amount of fibroplasia and angiogenesis necessary for the reestablishment of organ integrity. Such tissue contraction occurs over hours or days, a much slower time course than the rapid, reversible contraction of muscle tissue. Fibroblasts, which are rich in f-actin bundles, appear to be responsible for wound contraction. However, the signals that stimulate contraction are not known. Using cultured fibroblasts, which are also rich in f-actin bundles, we demonstrate the platelet and monocyte isoforms of platelet-derived growth factor (PDGF; AB and BB) but not PDGF-AA, can stimulate fibroblasts to contract collagen matrix in a time course similar to that of wound contraction. In addition, PDGF appears to be the predominant fibroblast/collagen gel contraction activity released from platelets. Vasoactive agonists known to stimulate smooth and striated muscle contraction do not stimulate fibroblast-driven collagen gel contraction.

Actin Cytoskeleton↗

Physiologic and plasma hormone correlates of survival in endotoxic dogs: effects of opiate antagonists.

Two groups of awake dogs were given an iv bolus of endotoxin (3.0 mg/kg from Salmonella typhimurium); one group (n = 9) was pretreated with either naloxone (2.0 mg/kg iv bolus with 1.7 mg/kg.h; n = 6) or naltrexone (2.0 mg/kg iv bolus with repeat bolus of 1.0 mg/kg at 1, 3 and 5 h; n = 3) and the second group (n = 10) received no opiate antagonist. All of nine dogs that were pretreated with an antagonist survived for 24 h, compared to only five of ten dogs that were not pretreated. Survival correlated with improved BP (mean of 91 vs. 61 mm Hg) and cardiac output (3.9 vs. 2.45 L/min) measured during the first 3 h after the infliction of shock. However, both antagonist-treated and nonantagonist-treated survivors had BP and cardiac output which were statistically lower than their baseline values or saline-treated controls at comparable times. Nonsurvivors had significantly higher levels of norepinephrine (peak level: 1149 ng/ml) and epinephrine (peak level: 31.29 ng/ml) than survivors. Opiate antagonists thus appeared to increase survival in a subgroup of dogs that might not otherwise have survived if they had not been so treated; this survival was associated with improved hemodynamics, but not with increased adrenergic activity.

Adrenocorticotropic Hormone↗

Comparative effects of cholera toxin, Salmonella typhimurium culture lysate, and viable Salmonella typhimurium in isolated colon segments in ponies.

Isolated segments of left dorsal colon and a side-to-side colocolostomy (between the left ventral colon and left dorsal colon) were surgically created in 6 adult ponies. Four segments, each separated by an empty segment, were inoculated (20 ml) with 1 of the following 4 solutions: phosphate buffered saline solution (PBSS)/1% polyethylene glycol (PEG); purified cholera toxin in PBSS/1% PEG (5 micrograms cholera toxin/ml of PBSS/1% PEG); lyophilized Salmonella typhimurium UCD 1755 culture lysate, reconstituted in PBSS/1% PEG; and viable S typhimurium UCD 1755 (10(8) organisms/ml of PBSS/1% PEG). Twenty hours following inoculation of the treatment solutions into the isolated colon segments, the ponies were reanesthetized. Fluid accumulation in the isolated segments was measured, and tissue samples from isolated segments were taken for examination by light microscopy and electron microscopy, and for measurement of mucosal cyclic adenosine monophosphate levels. There was fluid accumulation in segments inoculated with cholera toxin in 4 ponies (29.5 +/- 12.7 ml), and in segments inoculated with S typhimurium UCD 1755 culture lysate in 3 ponies (14.0 +/- 8.7 ml). There was no fluid accumulation in segments inoculated with either the control solution (PBSS/1% PEG) or viable S typhimurium UCD 1755. There was significantly (P less than 0.05) less cyclic adenosine monophosphate in segments inoculated with cholera toxin, Salmonella lysate, and viable Salmonella, compared with control segments. Histologically, there were minimal changes in control segments, consisting of mild to moderate submucosal edema and capillary congestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of thoracic aortic occlusion and cerebrospinal fluid drainage on regional spinal cord blood flow in dogs: correlation with neurologic outcome.

We studied the effect of thoracic aortic occlusion and cerebrospinal fluid (CSF) drainage on regional spinal cord blood flow and its correlation with neurologic outcome. Using isotope-tagged microspheres, we determined blood flow to the gray and white matter of five regions of the spinal cord in dogs: group I (control), group II (cross-clamp only), group III (cross-clamp plus CSF drainage). At 60 minutes after thoracic aortic occlusion in group II, median gray matter blood flow (GMBF) in the lower thoracic and lumbar cord decreased from 23.1 and 27.0 ml/100 gm/min at baseline to 4.0 and 2.5 ml/100 gm/min, respectively. The addition of CSF drainage improved GMBF during aortic cross-clamping in the lower thoracic and lumbar cord to 11.3 (p less than 0.05) and 15.1 ml/100 gm/min (p less than 0.03), respectively. After removal of the aortic cross-clamp, median blood flow more than tripled from baseline blood flow in group II, whereas CSF drainage prevented significant reperfusion hyperemia. Both low GMBF during cross-clamping and reperfusion hyperemia were associated with a worse neurologic outcome. In group II, no dog was neurologically normal, and more than 60% of the dogs had spastic paraplegia. In contrast, almost 60% of dogs in group III were normal, and none had spastic paraplegia (p less than 0.001). We conclude that CSF drainage in dogs during thoracic aortic occlusion maintained spinal cord perfusion above critical levels, diminished reperfusion hyperemia, and improved neurologic outcome.

Animals↗

Two classes of PDGF receptor recognize different isoforms of PDGF.

Previous studies involving platelet-derived growth factor (PDGF) have been based on the premise that a single cell-surface receptor binds all three isoforms of PDGF (AA, BB, and AB). It is now shown that two populations of PDGF receptor exist and can be distinguished by their ligand binding specificity. The B receptor binds only the BB dimer, whereas the A/B receptor binds AA, BB, and AB dimers. Human dermal fibroblasts appear to express seven times as much B receptor as A/B receptor. The B receptor is responsible for most PDGF receptor phosphorylation.

Binding, Competitive↗

Megacolon with myenteric hypoganglionosis in a foal.

A 6-month-old Clydesdale filly had chronic abdominal distention and intermittent febrile episodes. Abdominal surgery revealed impaction of the right dorsal colon, which was relieved by evacuation of contents through an enterotomy. Four days after surgery, abdominal distention recurred and progressed. The filly was euthanatized. Necropsy revealed the right dorsal colon to be markedly distended with digesta. Microscopically, there was a marked reduction in myenteric ganglion cells in the right dorsal colon and cecum and mild to moderate reduction of myenteric ganglion cells in the left ventral and transverse colon.

Animals↗

Megaesophagus and aspiration pneumonia secondary to gastric ulceration in a foal.

A 3-month-old foal with a history of persistent fever and leukocytosis was found to have pneumonia, ulceration of the squamous portion of the stomach, and dilatation of the distal portion of the esophagus. The foal was euthanatized and necropsied. The distal portion of the esophagus was severely dilated, and there was severe ulceration and mural thickening of the stomach at the cardia. Because of the severe gastric ulceration and mural thickening, the gastroesophageal junction was fixed in an open position, permitting gastroesophageal reflux. The megaesophagus and pneumonia were considered to have resulted from chronic gastroesophageal reflux.

Animals↗

Nutritional assessment of intensive-care unit patients.

The decision about whether to institute aggressive nutritional support, with its attendant expense and potential morbidity, in critically ill patients remains controversial. We studied numerous commonly used variables for assessment of nutrition to identify critically ill patients at increased risk for the development of infection, for becoming ventilator dependent, and for mortality. We enrolled 111 patients in this study on their third day in the intensive-care unit (ICU). No attempt was made to influence nutritional support, nor was adequacy of such support studied. Although several measurements correlated with outcome, the serum albumin correlated with number of ICU days (r = -0.38; P less than 0.001), with the number of days on a ventilator, and with the number of hospital days. It was the only measurement that correlated with the development of both a new infection (P less than 0.05) and ventilator dependency (P = 0.002). Although the use of the serum albumin concentration in this setting has limitations, it is still the best, most commonly used measurement of nutrition available.

Adult↗