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Biomedical subjects

L Davis

Publications and source records attributed to L Davis.

At least 109 records · Page 6Linked to original sources

Supplementary enteral nutrition maintains remission in paediatric Crohn's disease.

BACKGROUND: Liquid diets given enterally combined with "bowel rest' are efficacious in the treatment of active Crohn's disease, but rapid recrudescence of gastrointestinal symptoms after resumption of a normal diet is common. AIMS: This study examined whether continuation of enteral nutrition as a nocturnal supplement to an ad libitum daytime intake of a normal diet increased the length of remission of Crohn's disease in children. PATIENTS AND METHODS: Children and adolescents with active Crohn's disease treated successfully with exclusive enteral nutrition were classified retrospectively according to whether they continued supplementary enteral nutrition or not. Time to relapse and linear growth were compared between the two cohorts. RESULTS: Between January 1986 and December 1992, 65 patients aged 7-17 years (mean (SD) 13.6 (2.1) years) (36 males, 29 females) with Crohn's disease in exacerbation were treated for > or = four weeks by bowel rest and nasogastric tube feeding of an oligopeptide or amino acid based formula. At first follow up visit, remission (fall in Paediatric Crohn's Disease Activity Index, PCDAI to < or = 20) was achieved in 47 of 65 (72%) patients. Subsequently, 20 of these 47 (43%) relapsed by six months and 28 of 47 (60%) by 12 months. Patients who continued nasogastric supplementary feeding (n = 28) after resumption of an otherwise normal diet remained well longer than those who discontinued nocturnal supplements completely (n = 19) (p < 0.02). Furthermore, continued use of nasogastric supplements before completion of puberty was associated with improved linear growth. CONCLUSION: After successful treatment of active Crohn's disease by exclusive enteral nutrition, supplementary enteral nutrition without restriction of normal diet is associated with prolongation of remission and improved linear growth in children and adolescents.

Adolescent↗

Differential localization of prostaglandin E receptor subtypes in human kidney.

Four prostaglandin E2 (PGE2) receptors designated EP1, EP2, EP3, and EP4 have been pharmacologically identified, cloned, and sequenced. The present studies determined the intrarenal distribution of these EP-receptor subtypes in human kidney using in situ hybridization with riboprobes for the human EP receptors. mRNA for the phosphatidylinositol hydrolysis-coupled EP receptor was highly expressed in cortical, outer medullary, and inner medullary collecting duct. RNA for the Gi-coupled EP3 receptor was primarily expressed in the cortical and outer medullary collecting duct, as well as in the medullary thick ascending limb; however, it was absent from the inner medullary collecting duct. Expression of mRNA for EP1 and EP3 in connecting segment could not be excluded. There was no expression of the GS-coupled EP2 receptor mRNA detected in human kidney by in situ hybridization; however, mRNA for the GS-coupled EP4 receptor was highly expressed in the glomerulus. These studies demonstrate distinct regions of intrarenal expression for the different EP receptors and suggest that each receptor subtype may modulate different aspects of renal function in humans.

Autoradiography↗

Pharmacological evaluation of novel Alzheimer's disease therapeutics: acetylcholinesterase inhibitors related to galanthamine.

Acetylcholinesterase (AChE) inhibitors from several chemical classes have been tested for the symptomatic treatment of Alzheimer's disease; however, the therapeutic success of these compounds has been limited. Recently, another AChE inhibitor, galanthamine hydrobromide (GAL), has shown increased clinical efficacy and safety. Using biochemical, behavioral and pharmacokinetic analyses, this report compares GAL with two of its analogs, 6-O-acetyl-6-O-demethylgalanthamine hydrochloride (P11012) and 6-O-demethyl-6-O[(adamantan-1-yl)-carbonyl]galanthamine hydrochloride (P11149), for their therapeutic potential. P11012 and P11149 were found to be potent, competitive and selective inhibitors of AChE, demonstrating central cholinergic activity, behavioral efficacy and safety. P11012 and P11149, though pharmacokinetic analyses, were shown to act as pro-drugs, yielding significant levels of 6-O-demethylgalanthamine. In vitro, 6-O-demethylgalanthamine was 10- to 20-fold more potent than GAL as an inhibitor of AChE, and it demonstrated greater selectivity for inhibition of AChE vs. butyrylcholinesterase. Like GAL, both P11012 and P11149 showed central cholinergic activity biochemically, by significantly inhibiting rat brain AChE; physiologically, by causing hypothermia; and behaviorally, by attenuating scopolamine-induced deficits in passive avoidance. In addition, GAL, P11012 and P11149 enhanced step-down passive avoidance, another measure of behavioral efficacy. By comparing efficacious doses with primary overt effects, P11012 and P11149 had better oral therapeutic indices than GAL. Oral pharmacokinetic analyses of GAL, P11012 and P11149 revealed differences. Although P11012 and P11149 exhibited similar area under the curve values, 191149 had slower, lower and more sustained concentration maximum levels. P11012 and GAL rapidly reached their concentration maximums, but GAL, in brain had the highest area under the curve and concentration maximum. Because of its composite profile, including duration of action, oral therapeutic index and pharmacokinetics, P11149 is considered the better therapeutic candidate for the treatment of Alzheimer's disease.

Alzheimer Disease↗

Stability of plasma GABA at four-year follow-up in patients with primary unipolar depression.

The biology of mood disorders involves gamma-aminobutyric acid (GABA), a neurotransmitter whose levels in plasma likely reflect brain GABA activity. Previous research has shown that a subset of patients with primary unipolar major depression have low plasma GABA levels, which parallels findings from studies of cerebrospinal fluid. We have completed a 4-year follow-up on 46 male patients with primary unipolar depression. Plasma levels of GABA were stable over this time. For the group, mean plasma GABA levels on follow-up did not change significantly from entry levels. Plasma GABA levels measured on follow-up were significantly (p < .001) correlated with entry levels. Patients with low plasma GABA levels (< 100 pmol/ml) on entry into the study were likely to remain low on follow-up, and patients with plasma GABA levels in the control range (> or = 100 pmol/ml) at entry similarly remained in this category (chi 2 = 7.23, p = .007). This was true whether or not the patient had recovered from depression on follow-up. Levels of plasma GABA did not significantly correlate with severity of depression at either entry (p = .40) or follow-up (p = .52), nor was there a significant correlation between change in plasma GABA and change in the 17-item Hamilton Depression Rating Scale score from entry to follow-up (p = .89). These data are consistent with the notion that plasma GABA is independent of clinical state in patients with primary unipolar depression. Low plasma GABA may be a trait marker of illness in a subset of patients with mood disorder.

Adult↗

2-Amino-3-ketobutyrate-CoA ligase from beef liver mitochondria: an NMR spectroscopic study of low-barrier hydrogen bonds of a pyridoxal 5'-phosphate-dependent enzyme.

A study of protons associated with low-barrier hydrogen bonds in 2-amino-3-ketobutyrate-CoA ligase (AKB-ligase, EC 2.3.1.29) by NMR is reported. Three resonances are observed in the range of delta H = 15-20 ppm when the NMR spectrum of AKB-ligase is recorded at 600 MHz. These low-barrier hydrogen bonds are associated respectively with a side chain proton, the PLP pyridinium ring nitrogen proton, and the PLP Schiff base proton at the active site of the ligase. The pyridinium proton has been assigned a chemical shift of 19.10 ppm and the Schiff base proton 14.90 ppm. The third low-barrier hydrogen bond associated proton resonating at 16.20 ppm is assigned to a proton of a side chain group. All three resonances disappear when pyridoxal phosphate is removed from the ligase. Consistent with NOE coupling, the side chain group proton should be close to the proton of the Schiff base nitrogen of the pyridoxal 5'-phosphate. The effects of temperature, pH, substrate, and NOE on the three resonances are also studied, in order to assign the protons. The three low-barrier hydrogen bonds described in this report may serve to anchor the cofactor in the active site of 2-amino-3-ketobutyrate-CoA ligase.

Acetyltransferases↗

An SH3 domain is required for the mitogenic activity of microinjected phospholipase C-gamma 1.

Phospholipase activity is elevated in dividing cells. In response to growth factor stimulation, phospholipase C-gamma (PLC-gamma) binds to activated tyrosine kinase receptors via SH2 binding domains, resulting in phosphorylation of PLC-gamma and activation of its enzyme activity. These observations suggest that PLC-gamma participates in the signal transduction pathway employed by growth factors to promote mitogenesis. Consistent with this hypothesis, microinjection of purified bovine PLC-gamma into quiescent fibroblasts has been previously reported to initiate a mitogenic response [Smith et al. (1989) Proc. Natl. Acad. Sci. 86, 3659]. We have reproduced this result using recombinant rat PLC-gamma protein. Surprisingly, however, a catalytically inactive mutant of PLC-gamma, H335Q, also elicited a full mitogenic response. The capacity to induce mitogenesis by microinjection of PLC-gamma was mapped to the 'Z' domain of the protein, which contains PLC-gamma's SH2 and SH3 motifs. Inactivation of the phosphorylated tyrosine binding properties of both SH2 domains had no effect on the mitogenic activity of the Z-domain peptide. However, deletion of the SH3 domain resulted in a complete loss of activity. These results suggest that PLC-gamma's mitogenic properties do not require the enzyme's phospholipase activity, but are instead mediated by a novel pathway for mitogenic stimulation which is dependent upon an intact SH3 domain.

3T3 Cells↗

A Project Alpha program for smaller chapters.

Smaller chapters cannot easily adapt to their groups the projects of larger chapters or programs at the national level. To address this problem, the Coosa Valley chapter of AORN, Rome, Ga, developed a program that offers perioperative experience to nursing students at a local college. Members of the chapter act as preceptors for the students and educate them before the students' preceptorships in the OR. This education seems to relieve some of the intimidation and fear related to the OR, and students in the program are more willing to participate in the program.

Curriculum↗

The importance of monitoring dialysis adequacy in chronic peritoneal dialysis.

The case of a patient who was noted to be malnourished but improved after his dialysis dose was increased is presented. This case and the discussion that follows emphasize the importance of proactively monitoring peritoneal dialysis adequacy and nutritional intake, supporting the notion that the dose of peritoneal dialysis is a major determinant of appetite and, consequently, of nutritional status. In the clinical setting, this influence is best indicated by changes in the serum albumin level and ultimately in long-term patient survival. The case discussion reviews the major principles and supporting literature, describing how we target peritoneal dialysis delivery and optimize nutritional status in an effort to reduce morbidity and mortality.

Adult↗

Comparative analysis of mouse NotI linking clones with mouse and human genomic sequences and transcripts.

NotI cleavage sites are frequently associated with CpG islands that identify the 5' regulatory sites of functional genes in the genome. Therefore we analyzed a sample of 22 NotI linking clones prepared from mouse brain DNA, to determine whether these mouse NotI site associated clones could be used for comparative analysis of mouse and human genomes by cross-reaction with both mouse and human genomic DNA and RNA in Southern and Northern hybridization. We further examined whether we could establish the identity of these clones with known genes by comparing the nucleotide sequences surrounding the NotI site with the GenBank database. We observed that 70% of the clones cross-hybridized with human DNA and that 4 of 11 tested clones (36%) detected a transcript in human HeLa cells RNA whereas 73% clones (8/11) detected transcripts in mouse RNAs from one or more organs. Single pass sequence analysis was successful on 16 of 19 clones. The GC content in these sequence was very high (48.8% to 73.8%) suggesting that 12 of 16 sequenced clones contained a CpG island. Three out of 19 clones showed significant similarity with previously analyzed mouse gene sequences in GenBank, including the mouse rRNA gene family, cathepsin and the scip POU-domain genes. In addition, two sequences showed significant similarity to the human and rabbit protein phosphatase 2A-beta subunit and the human transforming growth factor-beta. Thus, 5 of 16 clones showed homology with identified genes. These results and the recent work of using RLGS methods for genetic mapping indicate that NotI linking clones can be used to efficiently cross reference a comparative analysis of the mouse and human genomic maps.

Animals↗

Race, control, mastery, and caregiver distress.

This study investigated the relationship between race, psychological resources of sense of control and caregiver mastery, and distress outcomes of caregiver depression and role stain among 77 African American and 138 White spouse caregivers of persons with dementia. Patterns of association between psychological resources and caregiving distress outcomes varied by type of outcome. Sense of control had a direct negative relationship with depression. Caregiver mastery moderated the effects of stressors on depression and was the only significant psychological resource predicting role strain. Although African American caregivers were less likely to report caregiver depression and role strain, there were no race differences in the process influencing caregiver distress.

Aged↗

Using a group-oriented contingency to increase social interactions between children with autism and their peers. A preliminary analysis of corollary supportive behaviors.

The effects of a group-oriented contingency on the social and supportive interactions of three preschoolers with autism and their socially competent peers were examined. Children participated in daily manipulative play activities in groups of three (including one target child and two peers). A group reinforcement contingency increased all three target children's social interactions with peers (e.g., share, assistance, and play organizers) but produced few or no corollary supportive exchanges within the playgroups (e.g., one socially competent youngster tells another to "Ask [target child] to share the Lego toys with us"). After a withdrawal of treatment phase in which social interactions decreased to low levels, children were taught to direct supportive comments to other members of their playgroups. Following this brief training, the interdependent group contingency was reinstated to reinforce the share, assistance, and play organizer exchanges between the target children and peers. In addition to interacting with the target children, socially competent youngsters also used supportive prompts to facilitate the social exchanges between their remaining group members. Children's social and supportive interactions decreased and increased again during subsequent baseline and group contingency phases. These results are discussed with regard to the efficacy of group-oriented contingencies and the function of supportive peer behaviors.

Autistic Disorder↗

Planning for the future: the implementation of an automated clinical system.

Preparing for automation is as important to the whole automation process as choosing the correct system. Planning should start some time before actual purchase. Once the strategic planning is complete, staff can begin researching what applications are available, what they do, what vendors are reputable, etc. Then the agency can begin the actual implementation.

Ambulatory Care Information Systems↗

Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis.

The clinical presentation and outcome of 32 children with primary sclerosing cholangitis (PSC) are reviewed, the largest North American series. The majority of patients were diagnosed in their second decade (median age: 13 years). Four children presented before the age of 2 years, but none in the neonatal period. Seventeen patients had inflammatory bowel disease (IBD), all with colitis, 14 ulcerative colitis, and 3 Crohn's disease. Eight patients presented with chronic liver disease before clinical onset of IBD. Only 8 of 32 patients were jaundiced at presentation. Fifteen of 32 had a normal serum alkaline phosphatase (ALP) level at presentation. Nine children presented with features similar to those of autoimmune hepatitis. Cholangiography was performed in all cases and classified by a scoring system specifically developed for pediatric patients. Intrahepatic disease predominated; in only three cases a common bile duct stricture was identified requiring stenting. Findings on the initial liver biopsy were classified according to Ludwig's criteria for staging PSC: there were 15 biopsies in stages 1 to 2 and 17 biopsies stages 3 to 4. HLA class I and II antigens were determined in 27 patients. An increased incidence of HLA B8 and DR2(15) but not DRw52a (DRB3*0101) was found. Anti-neutrophil cytoplasmic antibody (ANCA) was positive in 10 of 24 patients tested. Survival analysis indicated that a later age at presentation, splenomegaly, and prolonged prothrombin time (PT) at presentation were significant contributors to the prediction of poor outcome (i.e., death or listing for transplantation). Liver transplantation was successfully performed in seven children. Physicians must maintain a high index of suspicion of PSC in any child or young adult presenting with chronic liver disease, especially in the presence of IBD, even with a normal serum alkaline phosphatase level.

Adolescent↗

Evaluation of neuromuscular effects and antagonism of rocuronium bromide: a preliminary report.

Twenty ASA I-II patients received either 2 or 3 x ED95 doses of rocuronium bromide during nitrous oxide, oxygen, propofol, fentanyl-based anaesthesia. The mean times to maximum block were 98 s and 74 s and the mean duration of clinical relaxation (recovery to 25% T1) was 35 min and 46 min following 620 micrograms kg-1 and 930 micrograms kg-1, respectively. Neuromuscular blockade was antagonized with either neostigmine or edrophonium from a twitch height of 25%. Although there was no significant difference between the recovery times neostigmine appeared to give more consistent antagonism of rocuronium-induced blockade.

Adolescent↗