Biomedical subjects
Publications and source records attributed to G Davidson.
Maintaining accurate controlled substance records need not deter a veterinarian from obtaining and using opiate analgesics and anesthetics. Paperwork and behavior requirements for ordering, receiving, storing, administering, dispensing, and prescribing controlled substances are described in detail. Important regulatory information resources are also listed.
BACKGROUND & AIMS: There is limited information about the motor mechanisms responsible for gastroesophageal reflux (GER) in children. The aim of this study was to evaluate the relationship between esophageal body and lower esophageal sphincter (LES) motor events and the occurrence of GER. METHODS: Concurrent esophageal manometry and pH monitoring was conducted for 4 hours postprandially in 37 children referred for evaluation of suspected pathological GER. Presence of esophagitis and/or abnormal esophageal acid exposure was used to classify patients into two groups: those with pathological GER (group A; n = 24) and those in whom GER was not confirmed (group B; n = 13). RESULTS: GER occurred during LES relaxations unassociated with swallowing within 5 seconds before and 2 seconds after the onset of LES relaxation in 58% (group A) and 69% (group B) of the analyzable episodes. These swallow-independent sphincter relaxations satisfied criteria for classification as transient LES relaxations. An additional 23% (group A) and 19% (group B) of reflux episodes could have been a result of transient LES relaxation associated with swallowing by chance. Persistent absence of LES tone was an infrequent association of reflux and was confined to group A patients (8% of episodes). CONCLUSIONS: Transient LES relaxation is the most important cause of GER in children. Absent basal LES pressure is a relatively infrequent cause of reflux and only in children with pathological GER.
BACKGROUND: Gastro-oesophageal reflux disease causes significant morbidity in premature infants, but the role of dysfunction of the lower oesophageal sphincter (LOS) in this condition is unclear. METHODS: Oesophageal manometry was performed after gavage feeding in 13 healthy preterm neonates (postmenstrual age > or = 33 weeks) with a perfused sleeve with side hole assembly. Swallow related (both single and multiple) and transient LOS relaxations (TLOSRs) were identified and the characteristics of these events defined. Reflux was identified with manometric criteria (common cavity episodes). RESULTS: Five hundred and eleven relaxation of the LOS were observed, 55% related to single swallows, 23% related to multiple swallows, and 22% TLOSRs. The time to maximal LOS relaxation was longer for TLOSRs than for single or multiple swallows (mean (SEM) 5.0 (0.3) s v 3.0 (0.1) s and 3.3 (0.1) s, p < 0.0001 and p < 0.005). The durations of multiple swallows and TLOSRs were longer than single swallows (12.2 (0.5) s and 11.2 (0.4) s v 5.3 (0.2) s, p < 0.0001). Most of the oesophageal body common cavity episodes (94%) occurred during TLOSRs. CONCLUSIONS: In healthy preterm infants (postmenstrual age > or = 33 weeks) the motor events associated with LOS relaxation were similar to those seen in healthy adults. TLOSRs may be an important mechanism of reflux in premature infants.
The peripheral resistance to flow through each arterial bed (in actuality, the entire pathway from the heart back to the pericardial sinus) and the mechanical properties of the seven arteries leaving the lobster heart are measured and compared. Resistance is inversely proportional to artery radius and, for each pathway, the resistance falls non-linearly as flow rate increases. The resistance of the hepatic arterial system is lower than that predicted on the basis of its radius. Body-part posture and movement may affect the resistance to perfusion of that region. The total vascular resistance placed on the heart when each artery is perfused at a rate typical of in vivo flow rates is approximately 1.93 kPa s ml-1. All vessels exhibit adluminal layers of fibrils and are relatively compliant at pressures at or below heart systolic pressure. Arteries become stiffer at pressures greater than peak systolic pressure and at radii greater than twice the unpressurized radius. The dorsal abdominal artery possesses striated muscle in the lateral walls. This artery remains compliant over the entire range of hemolymph pressures expected in lobsters. These trends are illustrated when the incremental modulus of elasticity is compared among arteries. All arteries should function as Windkessels to damp the pulsatile pressures and flows generated by the heart. The dorsal abdominal artery may also actively regulate its flow.
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G-proteins define both the pharmacological characteristics and the signalling pathways of G-protein-coupled receptors. Melatonin receptors have been shown to belong to this class of receptors through their sensitivity to modulators of G-protein function. This study reveals that 2-125I-iodomelatonin (125I-MEL) binding to different target tissues is differentially affected by agents which disrupt the G-protein cycle. GTP gamma S, pertussis (PTX) and cholera (CTX) toxins each reduce 125I-MEL binding to ovine pars tuberalis (oPT) and lizard brain membranes, whereas chicken brain is affected only by GTP gamma S (guanosine 5'-O-(3-thiotriphosphate)) and CTX. In contrast, high affinity binding of 125I-MEL in the ovine hippocampus was not affected by any of these agents. This finding, together with the fact that neural binding sites of the sheep brain were found to have markedly lower molecular mass than those of the oPT on native gel electrophoresis (365 vs 525 kDa), suggests that the neural 125I-MEL binding sites in sheep may not be G-protein coupled. Pharmacologically, however, the binding sites in the hippocampus and oPT could not be distinguished using 11 analogues of melatonin. Therefore, these data support the notion not only of multiple forms of melatonin receptor/G-protein complex, but of high affinity binding sites for 125I-MEL which do not display sensitivity to guanine nucleotides.
Conventional manometric techniques are unsuitable for studies in premature infants and small laboratory animals. We have therefore developed silicone rubber 5-lumen and 10-lumen micromanometric extrusions with an o.d. 2.0 mm and lumina of 0.35 mm i.d. This study evaluates the suitability of microextrusions for intraluminal perfusion manometry. Pressure offset, post-occlusion pressure rise rate and sphincter model studies were used to assess the manometric performance of the extrusions and a miniature sleeve sensor (25 mm long) at infusion rates of 0.01-0.1 mL min-1. Micro-extrusions (5-lumen/10-lumen, respectively) had offsets (per 100 cm of length) of 3.8/5.0 mmHg at 0.01 mL min-1 and 25.6/26.2 mmHg at 0.1 mL min-1 and rise rates (in 160 cm lengths) of 64/43 mmHg sec-1 at 0.01 mL min-1 and 330/224 mmHg sec-1 at 0.1 mL min-1. Infusion rates 0.025 mL min-1 produced rise rates 100 mmHg sec-1. The miniature sleeve sensor had minimal resistance to perfusion, rise rates of 3 mmHg sec-1 at 0.01 mL min-1 and 23 mmHg sec-1 at 0.1 mL min-1 and recorded pressure as accurately as a side hole. We conclude that the performance of micromanometric extrusions and sleeves is sufficient for intraluminal perfusion manometry.
Low blood pressure is reported in Down's syndrome (DS). To assess this and determine whether low pressure results from the disease or from long-term residence in hospital, we measured blood pressure with a random-zero sphygmomanometer in three groups of patients: 52 DS inpatients, 62 DS outpatients, and 60 outpatients with other forms of mental handicap. Relative to normal reference populations, blood pressure was low in both DS inpatients (systolic, score -33 mm Hg, P < .0001) and DS outpatients (-25 mm Hg, P < .0001). It was normal in non-DS outpatients (-4.0 mm Hg, P = .3). Blood pressure rose normally with age in the non-DS group but not in the DS group. We conclude that blood pressure is low in DS and that this is a feature of the disease rather than of the protected environment in which patients live. A mechanism related to trisomy 21 is likely, and there may be a link with Alzheimer's disease (AD) because blood pressure is also low in Alzheimer's and a high proportion of Ds patients develop this disease. If, as is likely, blood pressure is lowered in Alzheimer's by the neuropathy, the same neuropathy developing early in DS may also reduce blood pressure.
The Mel 1a receptor gene has recently been cloned and sequenced, and its product has been found to represent a new class of the G protein-coupled receptor superfamily. A unique aspect of its endogenous hormonal ligand, melatonin, is the prolonged duration (16 h) required to initiate appropriate photoperiodic responses in the animal. This study provides the first data on the transcriptional and translational regulation of this receptor in primary cultures of its native tissue, the pars tuberalis of the ovine pituitary. Using RNAse protection assays we show Mel 1a mRNA expression is rapidly induced through changes in intracellular cAMP levels. Forskolin enhances Mel 1a mRNA expression, whereas melatonin reverses this effect. RNA stability is also a factor, as Mel 1a mRNA expression decreases rapidly in the presence of actinomycin D. Although the expression of receptor protein is sensitive to forskolin stimulation, the lag between induction of mRNA and protein suggests that other factors (e.g. RNA splicing) contribute to functional receptor expression. Furthermore we observed that both mRNA and receptor protein levels increase spontaneously during primary culture, and these rises could be blocked by melatonin. A spontaneous rise in Mel 1a mRNA can also occur in serum-depleted cultures. In the absence of corresponding changes in cAMP, these results suggest not only that the Mel 1a receptor can autoregulate its own expression by an undefined pathway, but also they provide the first evidence that melatonin can act via a cAMP-independent signal transduction pathway to repress transcription in this tissue.
Determination of intestinal permeability by measuring nonmetabolized sugars has been used to assess the integrity of intestinal mucosa. We have developed and validated a modified HPLC method for determining the concentration of L-rhamnose, mannitol, and lactulose in urine, using an amine-modified silica column and refractive index detection. Probe sugars are simultaneously resolved within 18 min. The calibration curve for each sugar is linear to 20 mmol/L. The minimum detectable concentration of lactulose is 0.05 mmol/L. Recovery of probe sugars is between 99.3% and 105.1%. Overall precision (CV) of estimation of probe sugars ranges from 4.2% to 6.5%. In 14 urine samples from healthy children who ingested the test solution containing 1 g of L-rhamnose, 1 g of mannitol, and 5 g of lactulose, the 5-h urinary excretion ratios of lactulose/rhamnose and lactulose/mannitol were 0.047 +/- 0.018 and 0.021 +/- 0.010 (mean +/- SD), respectively. This method presents a rapid, convenient, and practical technique for determining intestinal permeability in clinical pediatric practice.
BACKGROUND & AIMS: Gastroesophageal reflux is a common problem in premature infants. The aim of this study was to use a novel manometric technique to measure esophageal body and lower esophageal sphincter pressures in premature infants. METHODS: Micromanometric feeding assemblies (OD, < or = 2 mm) incorporating 4-9 manometric channels were used in 49 studies of 27 premature neonates. Esophageal body motility was recorded at three sites for 20 minutes after feeding. Twenty attempts (one per minute) were made to stimulate swallowing via facial stimulation (Santmyer reflex). In 32 studies lower esophageal sphincter pressures were recorded (sleeve) for 15 minutes before and after feeding. RESULTS: Peristaltic motor patterns were less common than non-peristaltic motor patterns (26.6% vs. 73.4%; P < 0.0001) that comprised 31.1% synchronous, 34.6% incomplete, and 6.3% retrograde pressure waves. Reflex swallowing was elicited more frequently in neonates older than 34 weeks postconceptional age than in younger infants (33.4% vs. 20.4%; P < 0.05). Mean lower esophageal sphincter pressure was 20.5 +/- 1.7 mm Hg before and 13.7 +/- 1.3 mm Hg after feeding (P < 0.0005). CONCLUSIONS: Premature infants show nonperistaltic esophageal motility that may contribute to poor clearance of refluxed material. In contrast, the lower esophageal sphincter mechanisms seem well developed.
A 9-year-old boy with a 5-year history of severe protracted diarrhea requiring home parenteral nutrition and a 1 year history of abnormal liver function tests was admitted for duodenal, rectal, and liver biopsy. Duodenal biopsy results showed mild villus blunting, a mild lymphocytic infiltrate, and absent goblet cells. Paneth cells and endocrine cells could not be identified. Review of several previous biopsies showed an almost total absence of goblet cells by light microscopy. Anti-goblet cell antibodies of the immunoglobulin (Ig)G class were shown by immunofluorescence with a titer of 1:512. Histological examination of rectal mucosa also showed a total lack of goblet cells, orderly surface epithelial cells, and infiltration of the colonic crypts by lymphocytes. Immunoperoxidase staining of rectal mucosa showed increased numbers of lymphocytes with an excess of CD3+, CD45RO+ T cells, and increased numbers of B cells labeling with B1 and L26. Increased numbers of CD25+ (activated) lymphocytes were also observed. HLA/DR expression was striking and observed in both the crypt and surface enterocytes, as well as in the lamina propria. Immunological assessment of the patient showed an inverted CD4/CD8 ratio and IgA/IgG4 deficiency. The liver biopsy and radiological investigation were in keeping with chronic sclerosing cholangitis. Although a slight and transient improvement in histological appearances was observed with prednisolone there was no significant improvement of diarrhea. Trials of azothiaprine and oral cyclosporin did not result in clinical or histological improvement.
This essay aims to briefly summarise the collection of articles on confidentiality issues in psychology, and to highlight apparently conflicting opinions about the confidentiality rule. Conflicts are then analysed in terms of competing systems of ethics. Finally, the role for ethics education in psychology education and training is considered.
The nature of melatonin receptor-G-protein coupling in ovine pars tuberalis (PT) cells of the pituitary was addressed using cholera (CTX) and pertussis (PTX) toxins. ADP-ribosylation of ovine PT membrane proteins using 32P-NAD in the presence of CTX radiolabelled several substrates including 44, 51, and 60 kD proteins. Each were clearly distinct from the 40 kD substrate radiolabelled in the presence of PTX. Acute incubation of PT membranes with either toxin reduced the number of high affinity binding sites for 125I-MEL, although the magnitude of the inhibition was much greater for CTX (56%) than for PTX (20%). A CTX-sensitive component also mediates the inhibition of forskolin-stimulated cyclic AMP accumulation as pre-treatment of PT cells with CTX (5 micrograms/ml) for 16 h blocked this response. Gs alpha is a major substrate for ADP-ribosylation by CTX, and 16 h pre-treatment of PT cells with CTX (5 micrograms/ml) caused a down-regulation of Gs alpha. Northern analysis showed only one major transcript of Gs alpha of about 2 kb, which would encompass all of the known splice variants of the Gs gene. Screening of a cDNA library from ovine PT for Gs-related genes and sequencing of clones, combined with RT-PCR of PT mRNA, revealed no novel products. On this basis it is concluded that the CTX substrate is unlikely to be a novel splice variant or related gene product of the Gs class of G-protein.(ABSTRACT TRUNCATED AT 250 WORDS)
The potential role of phospholipases in mediating melatonin-dependent inhibition of adenylyl cyclase was investigated in pars tuberalis (PT) cultures. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulated the release of choline metabolites and increased the transphosphatidylation reaction. The calcium ionophore A23187 stimulated the release of arachidonic acid from cultures. These observations demonstrate phospholipase A and D activities within PT. Phosphatidic acid inhibited forskolin-stimulated production of cyclic AMP both in PT cells and in membrane preparations. This indicates that melatonin could inhibit adenylyl cyclase by increasing phosphatidic acid levels through activation of cellular phospholipases. Melatonin did not stimulate the release of arachidonic acid or choline from PT cultures, nor did it increase intracellular levels of hydrophobic second messengers or stimulate transphosphatidylation. Therefore melatonin does not stimulate phospholipase A and D pathways in PT cells. However, these pathways are present in the PT and their activation could potentially modulate the cellular actions of melatonin.
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The function of the pars tuberalis as a mediator of the action of melatonin remains elusive. As a direct method of assessing the potential role of secretory proteins, ovine pars tuberalis cells have been cultured and radiolabelled with 35S-methionine, and the accumulation of specific radioactive products in the medium, measured after separation by SDS-PAGE and fluorography. The synthesis and secretion of a number of labelled proteins are increased by forskolin (1 microM) and inhibited dose dependently by melatonin (IC50, 300 pM), although consistently a 72-kD protein (p72), is the most intensely labelled of these. Thus, 72 acts as a useful marker of cellular activity for melatonin, whereas prolactin (p23) provides a melatonin non-responsive marker in ovine pars tuberalis cell cultures. The synthesis and secretion of p72 and other melatonin-sensitive proteins is regulated through the cyclic AMP/protein kinase A second-messenger pathway, as analogues of cyclic AMP mimic the action of forskolin, yet 1,9-dideoxyforskolin, a forskolin analogue that is not active on adenylate cyclase, has no effect. However, the phorbol ester, phorbol-12,13-myristate acetate, also regulates the synthesis and secretion of the same profile of proteins as forskolin indicating a potential role for protein kinase C, which occurs through an independent rather than a synergistic pathway. The differential effects of nocadazole (1 microM) and extracellular calcium depletion upon p72 and prolactin secretion indicates that p72 is secreted by a calcium and microtubule independent pathway, in contrast to prolactin. These observations in conjunction with the absence of dense-core storage vesicles in melatonin-responsive cells of the ovine PT are consistent with constitutive secretion of p72 from the latter and regulated secretion of prolactin from melatonin non-responsive cells. Using immunoprecipitation de novo synthesis and secretion of either LH or LH-like proteins from ovine pars tuberalis cells could not be detected under the conditions used. The absence of 125I-(Des-Gly10[D-Ala6]-LHRH-ethylamide) binding over most, but not all, of the ovine pars tuberalis supports the contention that the majority of the cells of the ovine pars tuberalis are not gonadotrophs. These results provide further support for the unique function for the pars tuberalis.
A new member of the G protein-coupled receptor superfamily has been isolated from an ovine genomic library with a probe generated by the application of the PCR technique, using cDNA synthesized on a mRNA template isolated from the ovine pars tuberalis. This genomic clone encodes a novel receptor of 325 amino acids with seven transmembrane domains. These domains share homology with other members of this family, but the best homology is with the recently cloned human MC-1 (50% in the transmembrane domains) and MC-3 (69% in the transmembrane domains) MSH receptors and the human ACTH (42% in the transmembrane domains) receptor. When this receptor was expressed in Cos7 cells, it was able to bind a potent analogue of alpha-MSH, [Nle4,D-Phe7]-alpha-MSH (NDP-MSH), with high affinity. This binding could be displaced by pro-opiomelanocortin-derived and related peptides, with the order of potency NDP-MSH > alpha-MSH = ACTH > beta-MSH and with no effect of gamma-MSH, delta-MSH or beta-endorphin. The expressed receptor was demonstrated to be functionally coupled to the adenylate cyclase second messenger pathway, with alpha-MSH, beta-MSH and ACTH stimulating cyclic AMP production. The amount of the mRNA for this receptor was found to be very low. The tissue distribution of this receptor could only be observed using the reverse transcription-PCR technique and the receptor was found to be present in a number of somatic tissues. These data indicate that this is a new and distinct member of the melanocortin receptor family.