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Biomedical subjects

M J Murray

Publications and source records attributed to M J Murray.

At least 19 recordsLinked to original sources

Statistical processing of large image sequences.

The dynamic estimation of large-scale stochastic image sequences, as frequently encountered in remote sensing, is important in a variety of scientific applications. However, the size of such images makes conventional dynamic estimation methods, for example, the Kalman and related filters, impractical. In this paper, we present an approach that emulates the Kalman filter, but with considerably reduced computational and storage requirements. Our approach is illustrated in the context of a 512 x 512 image sequence of ocean surface temperature. The static estimation step, the primary contribution here, uses a mixture of stationary models to accurately mimic the effect of a nonstationary prior, simplifying both computational complexity and modeling. Our approach provides an efficient, stable, positive-definite model which is consistent with the given correlation structure. Thus, the methods of this paper may find application in modeling and single-frame estimation.

Algorithms↗

The effect of a pectin-lecithin complex on prevention of gastric mucosal lesions induced by feed deprivation in ponies.

This study examined whether a product containing a pectinlecithin complex (Pronutrin) (1) could prevent gastric lesions induced in the equine gastric squamous epithelial mucosa using a protocol of intermittent feed deprivation that resulted in prolonged increased gastric acidity (Murray and Eichorn 1996). Eight ponies were used and served as their own controls in 2 trials in which there were 72 h cumulative deprivation (alternating 24 h with no feed, then 24 h free choice hay), with a 4-week interval between trials. Ponies were assigned randomly to receive either 250 g Pronutrin plus 200 g pelleted feed, or 450 g pelleted feed only. Ponies were conditioned to each treatment for 7 days and received Pronutrin and pellets or only pellets once daily during the feed deprivation protocol. Gastroscopy was performed at the beginning and conclusion of the feed deprivation protocol. The endoscopist (MJ.M.) was blinded as to treatments, and lesion severity was scored on a scale of 0-5. Gastroscopy revealed normal-appearing gastric mucosa at the beginning of feed deprivation, with the exception of 2 ponies which had focal squamous mucosal erosion and 1 pony with focal glandular mucosal erosion. After 72 h cumulative feed deprivation, each pony, except 1 pony in one of the trials, developed erosions or ulcers in the gastric squamous mucosa. There was no difference (P = 0.6) in the presence or severity of gastric lesions between treatments. Lesions did not develop in the gastric glandular mucosa as a result of the intermittent feed deprivation with either treatment. In this study, the pectin-lecithin complex in Pronutrin failed to prevent lesions in the gastric squamous mucosa induced by intermittent feed deprivation.

Animals↗

Isolation and characterization of Sarcocystis from brain tissue of a free-living southern sea otter (Enhydra lutris nereis) with fatal meningoencephalitis.

A protozoan was isolated in cell culture from the brain of a free-ranging sea otter with fatal meningoencephalitis. The biological history of this otter, a study animal being monitored via an intraperitoneal radio transmitter, is summarized. Histologically, protozoal parasites were associated with areas of brain inflammation and necrosis in the cerebrum and cerebellum. Morphology and measurements of fixed, Giemsa-stained protozoal zoites growing on coverslips were consistent with Sarcocystis. These parasites reacted only with polyclonal antisera raised against S. neurona on immunohistochemistry. Cell culture-derived zoites reacted strongly with polyclonal antiserum to S. neurona on indirect fluorescent antibody tests. Amplification of portions of the 18S ribosomal DNA and the adjacent first internal transcribed spacer were performed. The resulting sequences were compared with published sequences from similar apicomplexan protozoa. This isolate (SO SN1), was indistinguishable from S. neurona, based on parasite morphology, antigenic reactivity and molecular characterization.

Animals↗

Analgesic agents. Pharmacology and application in critical care.

Evaluation of analgesic agents is multifactorial. The authors know of no direct comparisons among the choices in analgesic agents that suggest one therapy over another in global outcomes such as mortality or morbidity. Therefore, until further outcome differentiation between agents is proved, understanding the primary difference of delivery routes, mechanisms of action, pharmacokinetics, and adverse effects serves as the best guide for selecting the appropriate agent for each patient.

Aging↗

Osteopontin and its receptor alphavbeta(3) integrin are coexpressed in the human endometrium during the menstrual cycle but regulated differentially.

Osteopontin is an arginine-glycine-aspartic acid-containing acidic glycoprotein component of the extracellular matrix that is postulated to bind to integrin receptors at the cell surface to mediate cellular adhesion and migration during embryo implantation. The primary aim of this study was to examine the uterine expression of osteopontin throughout the menstrual cycle in normal fertile controls sampled prospectively based on urinary LH surge detection. Expression of osteopontin was documented using Northern blot analysis, in situ hybridization, and immunohistochemistry. Furthermore, the temporal pattern of osteopontin expression was compared with that of its receptor, the alphavbeta3 integrin. Using Ishikawa cells, a well differentiated endometrial adenocarcinoma cell line, the in vitro regulation of osteopontin and its receptor alphavbeta3 integrin was studied. By Northern blot analysis, osteopontin mRNA appears during the early secretory phase, with maximal expression occurring in mid to late secretory-phase endometrium. The in situ hybridization analyses showed that osteopontin mRNA specifically localized in epithelial cells within the endometrium. Immunostaining of osteopontin was detected in the glandular secretions and on the apical portions of surface (luminal) epithelium. The patterns of expression of osteopontin by Northern blotting, in situ hybridization, and immunohistochemistry are remarkably similar to the pattern for the alphavbeta3 integrin. Despite these similarities in distribution, in vitro studies demonstrate that osteopontin and beta3 integrin subunit expression are differentially regulated. The expression of osteopontin was primarily induced in response to progesterone, whereas the beta3 integrin subunit was up-regulated by epidermal growth factor or heparin-binding epidermal growth factor. The differential regulation of these two endometrial proteins suggests the existence of two separate pathways regulating epithelial gene expression in human endometrium during the window of implantation. In adhesion assays using Ishikawa cells, alphavbeta3 but not alphavbeta5 or beta1 integrins appear to be the primary receptors for osteopontin. These findings may better define the factors that favor the development of a receptive endometrium.

Adult↗

A prospective, randomized study of endometrial telomerase during the menstrual cycle.

The purpose of this study was to characterize telomerase activity during the menstrual cycle, focusing on the luteal phase. A total of 84 endometrial biopsy samples were obtained from 72 participants. Daily urinary LH testing (OvuQuick, Quidel) was used to establish the day of the LH rise, and participants were randomized to return during the secretory phase. Twelve women returned on the identical day during the luteal phase of a subsequent cycle to allow intercycle comparisons of telomerase activity. Telomerase activity was evaluated using a modified TRAP-eze (Intergen) detection protocol. At the time of each endometrial biopsy, serum estrogen and progesterone were measured. Proliferative phase endometrium showed high telomerase activity. At the onset of the luteal phase telomerase activity was high, but it decreased during the early luteal phase, disappeared by the midluteal phase (6 d after LH surge detected), and then rose to moderate levels in the late luteal phase beginning on luteal d 10. Serum progesterone levels were inversely related to telomerase activity. In conclusion, endometrial telomerase activity is dynamic: high during the proliferative phase but inhibited during the midsecretory phase of the menstrual cycle. The timing of expression coincides with the rise and fall of progesterone levels and the time period of maximal uterine receptivity for embryo implantation. This supports a relationship between sex steroid levels and telomerase regulation.

Adult↗

Distribution of epidermal growth factor receptor (EGFr) in normal and acute peptic-injured equine gastric squamous epithelium.

Growth factors are important in healing and restoration of injured gastrointestinal tissues and, therefore, we characterised temporally the distribution and density of epidermal growth factor receptor (EGFr) in normal and peptic-injured gastric squamous epithelium of horses. Lesions were induced in the equine gastric squamous epithelium using a feed deprivation protocol that results in prolonged increased gastric acidity. Fifteen mature horses, 9 geldings and 6 mares, age 3 to 20 years, were used and divided into 3 groups: Group 1 (n = 5) were subjected to euthanasia for problems unrelated to the gastrointestinal tract and had normal-appearing gastric squamous mucosal epithelium; Groups 2 (n = 5) and 3 (n = 5) had lesions induced in the gastric squamous epithelium by alternating 24 h periods of feed deprivation and ad libitum access to hay, for a total of 48 h and 96 h, respectively. Following lethal injection of a barbiturate, stomachs were removed and fixed by filling with 4- 6 l 10% buffered formalin. Sections were made from normal stomachs and lesions in the gastric squamous epithelium adjacent to the margo plicatus along the right side of the stomach/greater curvature and the lesser curvature. A modified avidin-biotin immunoperoxidase technique was used to stain the formalin-fixed tissue specimens for EGFr. A computerised image analysis system was used to measure area occupied by EGFr (EGFr area) and mean EGFr density in 4 zones within the epithelium extending from the basal cell layers toward the lumen. Measurements were made of epithelium in an erosion bed, at the margin of an ulcer or erosion, and 10-15 mm distant from the lesion margin. Additionally, EGFr area and density were measured in epithelial cells adjacent to capillaries in the epithelium. Intermittent feed deprivation resulted in erosion and ulceration of the gastric squamous epithelium of each horse. Mean EGFr area and density were greatest (P<0.05) in the basal layer of epithelia from all horses, and EGFr staining diminished progressively toward the lumen. Tissues from Group 3 had significantly greater EGFr area in the lesion margin than epithelia from Group 2. EGFr density was less in the epithelia of erosion beds from Groups 2 and 3 compared to normal epithelium, and EGFr area in Group 2 erosion bed epithelia was significantly less than in normal epithelium and epithelia of Group 3. EGFr area in cells adjacent to epithelial capillaries of Group 3 was significantly greater than that of Group 1. Mitotic cell activity was significantly greater in epithelia associated with ulcers and erosions in Groups 2 and 3 compared to normal tissues from Group 1 horses. Staining for EGFr in the glandular mucosa adjacent to squamous epithelium at the margo plicatus was inconsistent and typically faint when present. EGFr distribution in equine gastric squamous epithelium was greatest in regions of greatest cell proliferation, and these areas were in the basal layers of epithelium and immediately adjacent to capillaries. There was evidence that EGFr is induced in peptic-injured equine gastric squamous epithelium. A receptor ligand, EGF or transforming growth factoralpha, may be a factor in healing of gastric squamous mucosal ulcers in horses. Further research should be directed at identifying this ligand and determining its origin in equine gastric mucosa.

Animals↗

Histological characteristics of induced acute peptic injury in equine gastric squamous epithelium.

The objective of the study reported here was to characterise the microscopic appearance of peptic-injured equine gastric squamous epithelium in relation to the duration of peptic injury. Erosions and ulcers were induced in equine gastric squamous epithelium using a feed deprivation protocol that results in prolonged increased gastric acidity. Specimens of normal gastric mucosa and mucosa with lesions created after 48 and 96 h of feed deprivation were compared for characteristics associated with angiogenesis and mucosal proliferation. Fifteen mature horses, 9 geldings and 6 mares, age 3-20 years, were divided into 3 groups. Group 1 (n = 5) had normal-appearing gastric squamous mucosal epithelium and had been killed due to problems unrelated to the gastrointestinal tract. Groups 2 (n = 5) and 3 (n = 5) had lesions induced in the gastric squamous epithelium by alternating 24 h periods of feed deprivation and ad libitum access to hay, for totals of 48 and 96 h feed deprivation, respectively. Following lethal injection of barbiturate, stomachs were removed and fixed by filling with 4-6 l 10% buffered formalin. Sections were made from lesions in the gastric squamous epithelium adjacent to the margo plicatus along the right side of the stomach/greater curvature and the lesser curvature. Measurements of total epithelial thickness, keratinised epithelium, nonkeratinised epithelium, epithelial projections, capillary extension into the epithelium and lamina propria thickness were made. The cross-sectional areas of arterial and venous vascular structures in the lamina propria at the lesions and their margins were measured using image analysis software. All horses, except one, in Group 2 developed erosions or ulcers in the gastric squamous epithelium after feed deprivation. There were several changes in the epithelium adjacent to erosions and ulcers, compared to normal epithelium, from horses in Groups 2 and 3: total epithelial thickness was significantly (P<0.05) greater, including both keratinised and nonkeratinised layers in most specimens; the length of epithelial projections and extent to which capillaries from the lamina propria extended toward the luminal surface, and the cross-sectional area of vascular structures (arterioles, capillaries, venules) in the lamina propria were significantly greater. Epithelial thickness of erosion beds was not significantly less than normal epithelium, although a greater proportion of the epithelium in erosions consisted of epithelial projections (Group 1, 23%; Group 2, 76%; Group 3, 72%). The cross-sectional area of vascular structures in the lamina propria beneath erosions was significantly greater than in normal mucosa only in Group 2 tissues, whereas in the lamina propria of ulcers it was significantly greater than in normal mucosa only in Group 3 tissues. The epithelial proliferation and increased vascular cross-sectional area in the lamina propria associated with peptic-induced gastric lesions are consistent with processes associated with the initiation of ulcer healing, and these changes temporally coincided with the initiation of peptic insult to the gastric squamous epithelium. These findings demonstrate that processes that promote ulcer healing begin soon after peptic injury and that they progress even with repeated peptic injury. Furthermore, our findings support observations that gastric ulcers often heal without medical intervention, and the theory that medications that reduce gastric acidity do not initiate healing, but rather facilitate ulcer healing by providing a microenvironment that is optimal for healing to proceed.

Animals↗

Cation metabolism during propofol sedation with and without EDTA in patients with impaired renal function.

OBJECTIVE: To compare the effects of propofol with and without disodium edetate (EDTA) on cation metabolism in intensive care unit (ICU) patients with renal insufficiency who received propofol or propofol plus EDTA (propofol EDTA) for sedation and mechanical ventilation. DESIGN: Double-blind, randomised, multicentre study. SETTING: Medical and surgical ICUs from 5 hospitals. PATIENTS: Thirty-nine ICU patients with acute and chronic renal impairment expected to require at least 24 hours of continuous sedation and respiratory failure necessitating mechanical ventilation. INTERVENTIONS: Propofol or propofol EDTA administered for sedation by continuous intravenous infusion. MEASUREMENTS AND RESULTS: The depth of sedation, as measured by the Modified Ramsay Sedation Scale, was similar in the 2 groups, when adjusted for dosing differences. The amount of propofol required to maintain adequate sedation was decreased in both groups compared to propofol requirements in ICU patients with normal renal function. EDTA levels were elevated at baseline in both groups. In the propofol EDTA group, the EDTA levels increased further by 20 % but decreased to below baseline EDTA levels at 48 hours after sedation. In the propofol group, EDTA levels decreased during sedation and remained below baseline levels at 48 hours after sedation. PATIENTS in both groups were hypocalcaemic and hyperphosphataemic at baseline with low levels of 1,25-dihydroxyvitamin D and elevated parathyroid hormone (PTH) levels. Other than a slight difference in ionised serum calcium levels at 4 h after the start of sedation, there were no significant differences observed in serum calcium levels between the two groups. There were no significant differences in 1,25-dihydroxyvitamin D or PTH levels over time between the two groups. There was no significant effect on renal function in either group. CONCLUSIONS: The results of this study suggest that adding EDTA to propofol does not adversely affect cation homeostasis or renal function when used for sedation of ICU patients with renal insufficiency. Although EDTA levels increased over time from baseline levels in patients with renal insufficiency who receive propofol EDTA, this increase does not appear to be clinically significant, and EDTA levels return to below baseline levels within 48 hours of discontinuing the propofol EDTA infusion. The efficacy of propofol with and without EDTA also appears comparable in these patients.

Adolescent↗

Critical care and perioperative medicine. How goes the flow?

The specialty of anesthesiology is at a crossroad. Do anesthesiologists stay in the illusionary safe harbor of the operating room and allow critical care anesthesiologists to float alone? How can in-fighting with other medical and nonmedical providers be avoided, while maintaining or expanding the historic and hopefully future roles of anesthesiologists as hospital-based physicians? A different tact is required to redefine the scope of the practice with broadened training to provide increased expertise in the evolving medical marketplace. This approach would include solid training in business, informatics, data management, and critical thinking on outcomes. This paradigm shift may be challenging, and requires redirection, reallocation of assets, re-education, and a new mindset. If successfully applied, however, it presents a means to strengthen the respected position of the specialty and to promote the medical care and practice of perioperative specialists in the rapidly changing landscape of modern medicine. Regarding the question of turf and ownership of the ICU, the authors suggest pursuing the higher ground of an excellent scope of practice, which facilitates the care and activities of surgical and primary care colleagues. These colleagues, administrators, and governmental agencies will have to be re-educated to support training and provide equitable remuneration. Appropriately trained anesthesiologist-intensivists can complement many other care providers, while providing a wide range of services with an economy of care, whether in a semiclosed or closed ICU setting.

Anesthesia Department, Hospital↗

Death related to propofol use in an adult patient.

OBJECTIVE: To report an adult trauma patient fatality related to propofol administration. DESIGN: Retrospective case review. SETTING: Trauma intensive care unit (ICU) in a level one trauma center. PATIENT: An 18-yr-old man involved in a motor vehicle crash. INTERVENTIONS: Treatment for multiple trauma injuries and propofol sedation. MEASUREMENTS AND MAIN RESULTS: Posttrauma ICU monitoring was performed. The patient developed cardiac arrhythmia, metabolic acidosis, and cardiac failure, which resulted in death. CONCLUSION: Death related to propofol infusion can occur in adults as well as in pediatric patients.

Acidosis↗

Dysregulated expression of ebaf, a novel molecular defect in the endometria of patients with infertility.

We recently described the expression of ebaf, a novel member of the transforming growth factor-beta superfamily in human endometrium. ebaf messenger ribonucleic acid was expressed in late secretory and menstrual endometria. Here, we show that ebaf is secreted as 42-, 34-, 28-, and 14-kDa proteins into the conditioned medium of transfected cells, endometrial fluid, and serum. The amount of secreted proteins was markedly reduced during the implantation window in the endometria and sera of normal fertile subjects. The expression of ebaf was dysregulated in the endometria of a subset of women with infertility during the receptive phase of the menstrual cycle. Abundant secreted protein was present in the endometria of these women during the implantation window. During the critical period of endometrial receptivity, ebaf protein was more abundant in patients with endometriosis who did not conceive than in patients who became pregnant. These findings show that ebaf is a secreted product and is released into body fluids. Some types of infertility are associated with dysregulated expression of ebaf in human endometrium, suggesting that a molecular defect in uterine receptivity may be identified using such a marker protein.

Adult↗

Effects of eicosapentaenoic and gamma-linolenic acids (dietary lipids) on pulmonary surfactant composition and function during porcine endotoxemia.

STUDY OBJECTIVES: To investigate whether a diet enriched with fish and borage oils, with their high polyunsaturated fatty acid (PUFA) content, alters surfactant composition and function during endotoxemia. DESIGN: Prospective, randomized, blinded, controlled animal study. SETTING: Research laboratory at a medical center. PARTICIPANTS: Thirty-six 15- to 25-kg, disease-free, castrated male pigs. DIETS AND MEASUREMENTS: Three groups of pigs (n = 12 per group) were fed for 8 days diets containing either omega-6 fatty acids (FAs) (corn oil; diet A), or omega-3 FAs (fish oil; diet B), or a combination of omega-6 and omega-3 FAs (borage and fish oils; diet C). Eight of 12 pigs in each group received a 0.1-mg/kg bolus of Escherichia coli endotoxin followed by a continuous infusion (0. 075 mg/kg/h). One lung was subsequently isolated ex vivo, and pressure-volume curves were measured. The contralateral lung was lavaged, and surfactant was analyzed for total and individual phospholipids and FA composition. Minimum and maximum surface tension was measured by bubble surfactometry. RESULTS: Pigs fed either diet B or C had increased oleic acid (C(18:1) omega-9), eicosapentaenoic acid (EPA; C(20:5) omega-3), docosahexaenoic acid (C(22:6) omega-3), and total omega-3 and monounsaturated FAs in their surfactant PUFA pools. The relative percentage of linoleic acid (C(18:2) omega-6) and total omega-6 FAs were significantly lower from pigs fed diets B and C compared with diet A. Palmitic acid (C(16:0)) concentrations, the primary FA in surfactant, had a tendency to be lower in pigs fed diets B and C. There were no demonstrable effects on surfactant function or pulmonary compliance. CONCLUSIONS: Diets containing EPA or EPA and gamma-linolenic acid altered the PUFA composition of pulmonary surfactant, but without demonstrable effects on surfactant function during porcine endotoxemia.

Animals↗