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Biomedical subjects

R D Murray

Publications and source records attributed to R D Murray.

At least 91 records · Page 5Linked to original sources

Stable isotope model for assessing production of short chain fatty acids from colon-derived sugar: application in pigs.

Sugar reaching the colon because of intestinal maldigestion or malabsorption may be fermented to acetate and other short-chain fatty acids, resulting in stimulation of colonic water absorption and cell proliferation. To explore this phenomenon in more detail, we have developed a stable isotope model for estimating the fraction of colon-derived glucose or lactose that is fermented to acetate, propionate and butyrate. In an initial application of the model, [d3]-acetate and either [1-(13)C]-glucose or [D-1-(13)C]-lactose were infused into the cecum or colon of piglets, and plateau plasma acetate enrichment was monitored in the carotid artery. In acutely anesthetized piglets, the fractions of glucose and lactose fermented to acetate were 17.0 and 20.0%, respectively. In a chronically catheterized piglet, fermentation was higher (34.2%). When conducted in chronically catheterized animals or via a colostomy or ileostomy in infants, this model may be used to determine how age, previous surgery or antibiotic therapy affects the efficiency of colonic assimilation of carbohydrate.

Acetates↗

Galactose-containing carbohydrates are preferentially absorbed in the neonatal pig colon.

Previous studies on the piglet colon in newborns cleared of bacterial metabolic activity showed a capacity for lactose absorption. Colonic absorption occurred at a flux rate equal to the assimilation of lactose by the small intestine but by a process that did not involve either glucose-galactose sodium cotransport or simple diffusion. Surprisingly, colonic lactose transport did not require either fermentation or cleavage of the disaccharide for uptake. Experiments were designed to test the selectivity of the colonic transport process for a variety of carbohydrates. Colonic tissues from 4-7-d-old piglets were mounted in Ussing chambers and the mucosal-to-serosal flux of radiolabeled carbohydrates was compared with that of lactose. The results showed a 3-4-fold greater flux of galactose-containing sugars as compared with glucose-containing carbohydrates at concentrations up to 40 mM. Even lactulose, a synthetic disaccharide assumed to require bacterial digestion before assimilation, was transported readily. N-Acetylgalactosamine, a component of colonic mucus, inhibited the flux of lactose, whereas N-acetylglucosamine did not. Similarly, lactosylated BSA inhibited lactose flux, whereas nonlactosylated BSA did not. The capacity of the colon of the newborn to differentiate moieties as similar as glucose and galactose suggests an absorptive process for carbohydrates with a high degree of discrimination.

Animals↗

Differentiating cyclic from chronic vomiting patterns in children: quantitative criteria and diagnostic implications.

OBJECTIVE: To establish criteria to differentiate two patterns of vomiting and to identify the predominant diagnoses for each group. METHODS: All children 2 to 18 years of age referred to a pediatric gastroenterology service who presented with recurrent vomiting (three episodes of vomiting within a 3-month period) as a primary complaint from 1985 to 1991 were retrospectively reviewed (n = 106). The vomiting pattern (emeses per hour and episodes per month), diagnostic studies, and therapeutic responses were compared by Mann-Whitney U and chi-squared tests. RESULTS: Based on the criteria of peak intensity (four or more emeses per hour) and frequency (nine or fewer episodes per month), two subgroups were differentiated: chilcren with a cyclic pattern (n = 34), who vomited at a higher peak intensity (12.6 +/- 1.6 vs 1.5 +/- 0.1 emeses per hour) but at a lower frequency (1.9 +/- 4.8 vs 36.6 +/-0.3 episodes per month) than those with a chronic pattern (n = 72). Among children with a cyclic patern, nongastrointestinal (65%) causes, especially peptic and infectiouus disorders, predominated over nongastrointestinal ones (10%). CONCLUSIONS: On the basis of quantitative historical criteria, children with recurrent vomiting can be classified into two subgroups that seem to be clinically and etiologically distinct. Abdominal migraine was the dominant diagnosis in those with cyclic vomiting, whereas peptic and infectious gastrointestinal disorders predominated in those with chronic vomiting. This differentiation between cyclic and chronic patterns of vomiting may be a useful diagnostic clue to the clinician.

Child↗

A portable device for estimating the rate of CO2 production in preterm infants.

We developed a simple flow-through system for measuring the net rate of pulmonary excretion of CO2 (VCO2). Its components, connected in series by plastic tubing, are the following: plastic oxygen hood, suction flask used both as a mixing and sampling chamber, Brooks mass flow controller, and wall suction. Gas aliquots withdrawn from the sampling flask are analyzed for CO2 concentration in the laboratory. The system was validated by measuring over a 60-min period the evolution of CO2 from the reaction of sodium carbonate with phosphoric acid. In 9 trials, the mean recovery of CO2 was 99.8%. In 14 studies in 11 preterm infants, we evaluated the reproducibility of duplicate measurements of CO2 production on consecutive days; in 9 of the studies, the coefficient of variation was < 5%, but in other 5 studies, it ranged from 7.7 to 35.8%. We believe that this device might have both research and clinical applicability.

Carbon Dioxide↗

Behaviour of dairy cows in a straw yard in relation to lameness.

Lying down and other behavioural activities of dairy cows were studied for three 24-hour periods in a straw yard. The cows spent a total of 13.6 hours in the straw yard and lay down for 9.7 hours. The lying down time in one observation was 10.8 hours and this period may be considered ideal because there was little disturbance during that observation. Significantly more time was spent lying down at night than in the day and significantly more time was spent lying down and ruminating than standing up and ruminating. The total time spent lying down was significantly positively correlated with the time spent lying down and ruminating. Ten hours or more spent lying down may be adequate for proper rest in dairy cattle. Straw yards are better than many cubicles for lying and a longer period spent lying down may be important for the prevention of lameness in dairy cows.

Animal Husbandry↗

Sedation with meperidine and midazolam in pediatric patients undergoing endoscopy.

We conducted a randomized, double-blind trial evaluating the efficacy and safety of meperidine 2 mg.kg-1 (M) and meperidine 2 mg.kg-1 plus midazolam 0.05 mg.kg-1 (M + M) in 40 pediatric outpatients (age 1 to 17 years) undergoing upper endoscopy procedures. The physician and nurse performing the procedure were asked to rate cooperation, emotional status, drowsiness, and overall efficacy. A blinded observer recorded the frequency of negative behaviors indicating distress, vital signs, and oxygen saturation before, during, and after the procedure. No significant differences were noted in the overall efficacy of the regimens. Good or excellent efficacy was noted in 15 of 21 children (71%) in the M group and 15 of 19 children (79%) in the M + M group by physicians; nurses assigned a good or excellent rating for 14 of 21 (67%) and 13 of 19 (68%) in the M and M + M groups, respectively. Immediately following the procedure, amnesia was noted in 4 of 17 (23%) patients who received M versus 14 of 18 (78%) patients who received M + M (P = 0.002). Of the children who received M + M, the amnesia tended to occur more frequently in older children (> 11 years, 8 children, rate of amnesia 100%) than in younger children (< or = 11 years, 6 of 10 evaluable children, rate of amnesia 60%). There was no significant difference between the frequency of negative behaviors, rate of adverse effects, or changes in vital signs or oxygen saturation noted with the two drug regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Observer variation in field data describing foot shape in dairy cattle.

A qualitative scoring method was devised to describe foot shape in dairy cattle, which relied solely on visual observations. Four independent trained observers used the method to assess the foot shape of 248 cows located on three farms on two different occasions, and the percentages of agreement and near-agreement for intraobserver and interobserver variation on scores for foot shape were calculated. Score assessment methods were suitable for describing features with a broad variation within one score value; reducing the number of observers did not improve best agreement between separate observations by more than 80 per cent.

Analysis of Variance↗

Gross and histopathological study of endotoxin-induced hoof lesions in cattle.

In young cattle infusion of Escherichia coli endotoxin resulted in sole and wall haemorrhages that were more severe in the hind than in the fore feet. Histopathological examination of biopsies taken 5 days after infusion showed separation at the tips of the laminae, changes in the vascularity of the dermal papillae and laminae, lightly stained material in the sole horn and degeneration of the epidermal cells of the laminae and papillae. Later, densely stained material in the tubules of the sole, arteriosclerosis in all parts of the corium and proliferative changes in the laminae were seen. It is concluded that endotoxin can induce diffuse aseptic pododermatitis in cattle, characterized by initial degenerative changes in the papillae and laminae followed by proliferative changes in the laminae and arteriosclerosis in all parts of the corium.

Animals↗

Central and peripheral actions of the novel kappa-opioid receptor agonist, EMD 60400.

1. The pharmacological characteristics of the kappa-opioid receptor agonist, EMD 60400, have been investigated, with particular reference to its central and peripheral sites of action and its ability to influence nociception. The kappa agonists ICI 197067 and ICI 204448 were tested for purposes of comparison. 2. EMD 60400 and ICI 197067 bind with high affinity (IC50 values of 2.8 and 1.5 nM, respectively) and high selectivity to kappa-opioid receptors. ICI 204448 has a lower binding affinity (IC50 13.0 nM) and selectivity for kappa-opioid receptors. 3. EMD 60400, ICI 197067, and ICI 204448 are full and potent agonists in the rabbit vas deferens in vitro assay for kappa-opioid receptors (IC50 values of 41.8, 15.7 and 15 nM, respectively). 4. Ex vivo binding experiments in mice revealed that EMD 60400 and ICI 197067 were well taken up after s.c. administration. Brain levels of EMD 60400 were lower than those of ICI 197067 at comparable doses, indicating that EMD 60400 does not penetrate into the CNS as well as ICI 197067. 5. Haloperidol-induced DOPA accumulation in the nucleus accumbens of the rat was dose-dependently reversed by s.c. application of EMD 60400 and ICI 197067 at doses of and above 3 and 0.3 mg kg-1, respectively. ICI 204448 had no effect on DOPA accumulation at 30 mg kg-1, s.c. 6. Prolongation of hexobarbitone-induced sleeping time in mice and motor impairment in the rat rotarod test were observed for EMD 60400 at doses above 3 and 2.5 mg kg-1, s.c., respectively, and for ICI 197067 at doses above 0.3 and 0.25 mg kg-1, s.c., respectively. ICI 204448 was inactive in these tests at doses of 30 and 100 mg kg-1, s.c., respectively.7. EMD 60400 applied s.c. produced dose-dependent naloxone-reversible antinociception in the mouse formalin test (1st and 2nd phase ID50 0.44 and 0.47 mg kg-1, respectively) and rodent writhing test (ID50 mouse 0.55 mg kg-1 and rat 0.3mg kg-1). Furthermore, EMD 60400 was considerably more potent in the rat pressure pain test after the induction of inflammation with carrageenin than under normalgesic conditions (ID50 values 0.1 Microg kg-1 and 4.0 mg kg-1, s.c., respectively). The action of EMD 60400 (50 microgkg-1, s.c.) in the hyperalgesic pressure pain test was completely antagonized by injection of the K-opioid antagonist, norbinaltorphimine (100 microg) into the inflamed tissue, thus demonstrating the peripheral opioid nature of this effect.8. EMD 60400 produced dose-dependent inhibition of neurogenic plasma extravasation elicited byantidromic electrical stimulation of the rat saphenous nerve (ID50 value 0.3 mg kg-1, i.v.). This inhibition was completely antagonized by intraplantar injection of norbinaltorphimine (50 microg).9. EMD 60400, ICI 197067, and ICI 204448 have diuretic effects in rats at doses of and above 0.1, 0.01,and 0.3 mg kg-1, s.c., respectively. An antidiuretic action was also observed with ICI 197067 at very low doses (3 and 6 microgkg-1, s.c.).10. Pharmacological and biochemical data therefore indicate that the three K-opioid receptor agonists tested here have different tendencies to elicit centrally-mediated sedation and putative aversion(ICI 197067 > EMD 60400 > ICI 204448) which correspond to their ability to cross the blood-brain barrier. EMD 60400 combines high affinity and selectivity for the K receptor with a degree of peripheral selectivity. The peripheral actions of systemically-applied EMD 60400 against hyperalgesic pressure pain and neurogenic inflammation are very probably mediated by opioid receptors on the endings of sensory nerve fibres.

Analgesics↗

A pharmacological profile of the novel, peripherally-selective kappa-opioid receptor agonist, EMD 61753.

1. The pharmacological properties of the novel diarylacetamide kappa-opioid receptor agonist, EMD 61753, have been compared with those of ICI 197067 (a centrally-acting kappa agonist) and ICI 204448 (a peripherally-selective kappa agonist). 2. EMD 61753 binds with high affinity (IC50 5.6 nM) and selectivity (kappa:mu:delta:sigma binding ratio 1:536:125: > 1,786) to kappa-opioid receptors and is a full and potent (IC50 54.5 nM) agonist in an in vitro assay for kappa-opioid receptors (rabbit vas deferens preparation). 3. Systemically-applied [14C]-EMD 61753 is found in high concentrations in the lungs, liver, adrenal glands and kidneys. Considerably less radioactivity is detected in the whole brain, and this radioactivity is concentrated in the region of the cerebral ventricles in the choroid plexuses. EMD 61753 penetrates only poorly into the CNS. 4. EMD 61753 was weakly effective in pharmacological tests of central activity. This compound reversed haloperidolol-induced DOPA accumulation in the nucleus accumbens of the rat only at a dose of 30 mg kg-1, s.c., (doses of 0.1, 1.0 and 10 mg kg-1, s.c., and 1.0, 10 and 100 mg kg-1, p.o., were inactive). Hexobarbitone-induced sleeping in mice was prolonged by EMD 61753 at threshold doses of 10 mg kg-1, s.c., and 100 mg kg-1, p.o., whereas the motor performance of rats in the rotarod test was impaired by EMD 61753 with an ID50 value of 453 mg kg-1, s.c. 5. EMD 61753 produced dose-dependent, naloxone-reversible antinociception in the mouse formalin test (1st phase ID50 1.9 mg kg-1, s.c., and 10.4 mg kg-1, p.o.; 2nd phase ID50 0.26 mg kg-1, s.c., and 3.5 mg kg-1, p.o.) and rodent abdominal constriction test (ID50 mouse 1.75 mg kg-1, s.c., and 8.4 mg kg-1, p.o.; ID50 rat 3.2 mg kg-1, s.c., and 250 mg kg-1, p.o.). EMD 61753 was inactive, or only weakly effective, in the rat pressure test under normalgesic conditions. After the induction of hyperalgesia with carrageenin, however, this compound elicited potent, dose-dependent (ID50 0.08 mg kg-1, s.c., and 6.9 mg kg-1, p.o., after remedial application, and 0.2 mg kg-1, s.c., and 3.1 mg kg-1, p.o., after prophylactic application) and naloxone-reversible antinociception. The antinociceptive action of systemically-applied (50 mg kg-1, p.o.) EMD 61753 in the hyperalgesic pressure test was completely inhibited by injection of the K-opioid antagonist norbinaltorphimine (100 Lg) into the inflamed tissue, a result which indicates that this opioid effect is mediated peripherally.6. Cutaneous plasma protein extravasation produced by antidromic electrical stimulation of the rat saphenous nerve was dose-dependently inhibited by systemically-applied EMD 61753 (ID13 values 3.7 mg kg-1, s.c., and 35.8 mg kg-1, p.o.), and this effect was completely antagonized by intraplantar application of norbinaltorphimine (50 microg). Extravasation elicited by the intraplantar application of substance P (10 microg) was not influenced by the administration of EMD 61753.7. EMD 61753 produced dose-dependent diuresis in non-hydrated rats at doses of and above 1.0 mg kg-1, s.c., and 10 mg kg-1, p.o., and in saline-loaded rats at doses of and above 10 mg kg-1, s.c.,and 30mgkg-1, p.o.8. The prostaglandin-mediated fall in mean arterial blood pressure elicited in anaesthetized rats by i.v.application of arachidonic acid was not inhibited by prior treatment with EMD 61753 (10mg kg-1,p.o.). Thus, a blockade of prostaglandin synthesis via inhibition of cyclo-oxygenase activity does not contribute to the in vivo effects of EMD 61753 and its metabolites.9 The present experiments therefore indicate that EMD 61753 is a potent, selective and orally-effective full ic-opioid receptor agonist which has a limited ability to penetrate the blood-brain barrier and elicit centrally-mediated sedation, putative aversion, diuresis, and antinociception. The inhibitory actions of systemically-applied EMD 61753 against hyperalgesic pressure nociception and neurogenic inflammation are mediated peripherally, probably by opioid receptors on the endings of sensory nerve fibres.

Acetamides↗

The effect of vaccination against Leptospira interrogans serovar hardjo infection at the time of service on pregnancy rates in dairy cows.

Fertility data from 16 dairy herds vaccinated against hardjo infection were used to assess pregnancy rates in cattle vaccinated around the day of mating. There was no improvement in pregnancy rates 30-60 d after vaccination. Pregnancy rates in the period 5 d before and 10 d after vaccination were statistically lower than those found in 30-60 d around vaccination.

Animals↗

Behaviour of first lactation and adult dairy cows while housed and at pasture and its relationship with sole lesions.

The times spent lying down and standing by first lactation and adult cows while they were housed and while they were at pasture were studied and related during the period of housing to the incidence of sole lesions in first lactation cows. First lactation cows lay down for a shorter time in the early housing period than later. First lactation and adult cows lay down for longer when at pasture. Maximum lying time was significantly longer and the frequency of lying lower on pasture than indoors. The times spent lying and standing and the frequency of lying were related to the incidence of sole lesions. Rumination time was not related to the occurrence of sole lesions although there were significant variations in rumination behaviour while the animals were housed and at pasture. The patterns of lying and other activities of first lactation and adult cows while they were housed were quite different from those while they were at pasture.

Animal Husbandry↗

Welfare implications of modern artificial breeding techniques for dairy cattle and sheep.

The legislation which protects animals from cruelty and poor welfare is described, from both a European and British perspective. Using well-established definitions of welfare, it can be seen that certain current practices related to farm animal breeding may constitute poor welfare particularly for dairy cattle. Taking only scientific measures of welfare as criteria for acceptable practice may not completely satisfy public concern over some biotechnical innovations in animal breeding. A reassessment of attitudes towards manipulation of animals for human use may be necessary.

Animal Welfare↗

Behaviour of lame and normal dairy cows in cubicles and in a straw yard.

The behaviour of normal cows in cubicles was compared with that of normal cows in a straw yard and that of lame cows in cubicles. The normal cows in a straw yard lay down for longer in total (9.6 hours vs 6.8 hours) and during the night (8.55 hours vs 4.75 hours) and for significantly longer at a time (3.95 hours vs 2.45 hours) than normal cows in cubicles. The normal cows in a straw yard spent more time lying down and ruminating (5.1 hours) than normal cows in cubicles (3.3 hours). Lame cows in cubicles lay down for significantly longer during the day (3.3 hours) than normal cows in cubicles (2.1 hours). Although lameness did not affect the total time the cows spent in feeding and rumination, lame cows moved about less, and they adopted abnormal postures suggesting discomfort.

Animal Husbandry↗

Effects of lameness on the behaviour of cows during the summer.

The welfare implications of lameness in dairy cattle are considerable, and in addition to causing great pain and discomfort to the animals it is detrimental to productivity. This study investigated the differences in behaviour of lame and normal cows during the summer. Their rank of entry and behaviour in the milking parlour were examined. Lame cows entered the parlour later than normal cows (P < 0.01), and were significantly more restless on their feet while being milked (P < 0.01). When cows were at pasture the lame cows lay down for longer (P < 0.01) and grazed for shorter periods than the normal cows (P < 0.01). All cows ruminated for longer periods when lying down than when standing, but the difference was significant only for the lame cows (P < 0.01). In addition, lame cows had significantly lower bite rates than normal cows (P < 0.01). The behavioural differences between lame and normal cows indicated that lameness had serious effects on the welfare and productivity of lame cows.

Animals↗

Reliability of echocardiographic measurements of myocardial perfusion using commercially produced sonicated serum albumin (Albunex).

OBJECTIVES: The purpose of this study was to assess the reproducibility and pitfalls of intracoronary and aortic root sonicated albumin injections, using time-intensity curves, in a large sample of normal dogs. BACKGROUND: The utility of a new myocardial contrast echocardiographic agent, sonicated serum albumin (Albunex), is currently under investigation. However, the reproducibility, injection techniques and general pitfalls of this contrast agent have not been well characterized. METHODS: We administered sequential intracoronary and aortic root injections (518 injections) of sonicated albumin in 25 closed chest normal dogs to measure the effectiveness and reproducibility of this product. Time-intensity curves, as a measure of myocardial perfusion, were derived and quantified using an on-line videodensitometric analysis system and two-dimensional echocardiography. Measurements included peak intensity, area under the curve, half-time of descent, alpha-parameter and transit time within a 31- x 31-pixel "region of interest" in the anterior septum. Analyses provided 80% power and a type I error protection of 95%. RESULTS: The best reproducibility of the variables was half-time of descent for aortic root injections (coefficient of variation [CV] 20%) and peak intensity for intracoronary injections (CV 25%), whereas aortic root area under the curve showed the most variability (CV 41%). Analysis of variance for repeated measures of serial intracoronary and aortic root injections showed no significant systematic variability within subjects for the measured variables. In a comparison between intracoronary and aortic root injection sites, paired t tests showed no significant difference for mean values between these two techniques. There was also no statistically significant difference between manual versus power intracoronary injections. Finally, there was no significant difference among three injection rates (1, 2 and 3 ml/s) in paired intracoronary injections, nor was there a difference among injection rates in paired aortic root injections, except for a lower peak intensity with a 1-ml/s injection rate compared with a 2-ml/s injection rate (p = 0.01). Potential pitfalls include preparation of sonicated albumin, delivery techniques and measurement variables. CONCLUSIONS: We conclude that the results of serial injections of sonicated albumin show no systemic change or trend in normal dogs. Both intracoronary and aortic root injections at standard injection rates by hand or power injector can be used to quantify time-intensity curves, as measure of myocardial perfusion, with similar variability ranging from 20% to 41%. These results are important in the human model, especially after coronary interventions.

Albumins↗

Efficacy of diazepam and meperidine in ambulatory pediatric patients undergoing endoscopy: a randomized, double-blind trial.

Medications are routinely administered to children prior to upper gastrointestinal endoscopy procedures. We evaluated the efficacy and safety of four dosage regimens: meperidine 2 mg/kg (M); low-dose meperidine 1 mg/kg and diazepam 0.1 mg/kg (M low+D); high-dose meperidine 2 mg/kg and diazepam 0.1 mg/kg (M high+D); and, diazepam 0.1 mg/kg (D) in a randomized, double-blind trial in 71 pediatric patients (ages 1 to 19 years). Cooperation, emotional state, and sedation were rated. The frequency of negative behavior demonstration (i.e., crying, gagging, flailing, nervous behavior) indicating ineffective or inadequate sedation was recorded before, during, and after the procedure. Vital signs and oxygen saturation were noted. Significant differences were observed in the efficacy of the various sedation regimens. Overall, the physicians and nurses rated M most effective in children < 11 years. In these children, M high + D and D were rated least effective by the nurses, whereas physicians felt that D was least effective. In the older children, M, M low + D, and M high + D were rated similarly effective by physicians and nurses, and D was rated least effective. In both age groups, the lowest incidence of negative behaviors during the endoscopy procedure occurred in patients who received M. Combinations of D and M + D resulted in an increased incidence of negative behaviors; thus, M may be the preferred sedation regimen in children undergoing endoscopy. The addition of diazepam to meperidine may be detrimental in terms of eliciting negative behaviors.

Adult↗