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Biomedical subjects

R E Nelson

Publications and source records attributed to R E Nelson.

At least 19 recordsLinked to original sources

Benchmarking in health-system pharmacy: experience at MeritCare Medical Center.

The experience of MeritCare Medical Center (MMC) with the Benchmarking Program coordinated by The Clinical Pharmacokinetics Laboratory at Millard Fillmore Hospital is described. MMC is a community-based teaching institution in Fargo, North Dakota, that serves patients in North Dakota, South Dakota, and Minnesota. MeritCare began participating in the Benchmarking Program in 1997. Data from the individual hospital report raised concern about the high cost of antimicrobials at MMC relative to peer-group institutions. The staff conducted an evaluation of antimicrobial prophylaxis for noncardiovascular surgery, concluded that cefazolin use was suboptimal, and attempted to encourage more cost-effective utilization. MMC's participation in the Benchmarking Program also prompted more appropriate use of various other antimicrobial agents, including i.v. and oral ciprofloxacin. An i.v.-to-oral switching program was begun for various agents. Preliminary analysis after 15 months demonstrated direct cost savings for drug acquisition of $60,000 to $80,000 per year and a reduced length of stay. Initiatives undertaken by MeritCare on the basis of data obtained through the Benchmarking Program resulted in substantial estimated savings in drug acquisition costs.

Anti-Bacterial Agents↗

Papilin in development; a pericellular protein with a homology to the ADAMTS metalloproteinases.

Papilin is an extracellular matrix glycoprotein that we have found to be involved in, (1) thin matrix layers during gastrulation, (2) matrix associated with wandering, phagocytic hemocytes, (3) basement membranes and (4) space-filling matrix during Drosophila development. Determination of its cDNA sequence led to the identification of Caenorhabditis and mammalian papilins. A distinctly conserved 'papilin cassette' of domains at the amino-end of papilins is also the carboxyl-end of the ADAMTS subgroup of secreted, matrix-associated metalloproteinases; this cassette contains one thrombospondin type 1 (TSR) domain, a specific cysteine-rich domain and several partial TSR domains. In vitro, papilin non-competitively inhibits procollagen N-proteinase, an ADAMTS metalloproteinase. Inhibiting papilin synthesis in Drosophila or Caenorhabditis causes defective cell arrangements and embryonic death. Ectopic expression of papilin in Drosophila causes lethal abnormalities in muscle, Malpighian tubule and trachea formation. We suggest that papilin influences cell rearrangements and may modulate metalloproteinases during organogenesis.

Amino Acid Sequence↗

An automated administration of Corsi's Block-tapping Test.

Corsi's Block-tapping Test has been a clinically useful test of visuospatial memory. Participants (15 men, 15 women) completed an automated and a manual version of the Block-tapping Test, the findings for which suggest that the automated and manual versions gave very similar scores.

Adolescent↗

Long-term pharmaceutical cost reduction using a data management system.

UNLABELLED: Cost containment is an important issue in medicine today, and the ability to control costs and maintain quality patient care presents a challenge to practitioners. Educating practitioners about drug costs has been identified as an effective method, but the benefits of education are usually short-lived. To evaluate the role of education in cost control, pharmaceutical use and performance improvement data were analyzed at a tertiary care institution during two time periods. A total of 4,530 anesthesia records and associated performance improvement data from March to June 1993 were analyzed as a baseline. These data were shared with the clinicians of an anesthesia department and used to educate practitioners regarding the costs and use of injectable pharmaceuticals and to identify areas in which cost savings could be achieved. The same information from 10,600 cases during January to October 1996 were compared with the early group. The expenditures for injectable pharmaceuticals to provide anesthesia were decreased by more than $30,000 per month, or $32 per case, without changing the performance indicators that were monitored, and has been maintained for >3 yr. IMPLICATIONS: By using a data management system, the cost for medications to provide anesthesia has been reduced without changing the quality of patient care.

Anesthesia↗

Drosophila UDP-glucose:glycoprotein glucosyltransferase: sequence and characterization of an enzyme that distinguishes between denatured and native proteins.

A Drosophila UDP-glucose:glycoprotein glucosyltransferase was isolated, cloned and characterized. Its 1548 amino acid sequence begins with a signal peptide, lacks any putative transmembrane domains and terminates in a potential endoplasmic reticulum retrieval signal, HGEL. The soluble, 170 kDa glycoprotein occurs throughout Drosophila embryos, in microsomes of highly secretory Drosophila Kc cells and in small amounts in cell culture media. The isolated enzyme transfers [14C]glucose from UDP-[14C]Glc to several purified extracellular matrix glycoproteins (laminin, peroxidasin and glutactin) made by these cells, and to bovine thyroglobulin. These proteins must be denatured to accept glucose, which is bound at endoglycosidase H-sensitive sites. The unusual ability to discriminate between malfolded and native glycoproteins is shared by the rat liver homologue, previously described by A.J. Parodi and coworkers. The amino acid sequence presented differs from most glycosyltransferases. There is weak, though significant, similarity with a few bacterial lipopolysaccharide glycotransferases and a yeast protein Kre5p. In contrast, the 56-68% amino acid identities with partial sequences from genome projects of Caenorhabditis elegans, rice and Arabidopsis suggest widespread homologues of the enzyme. This glucosyltransferase fits previously proposed hypotheses for an endoplasmic reticular sensor of the state of folding of newly made glycoproteins.

Amino Acid Sequence↗

Peroxidasin: a novel enzyme-matrix protein of Drosophila development.

Peroxidasin is a novel protein combining peroxidase and extracellular matrix motifs. Hemocytes differentiate early from head mesoderm, make peroxidasin and later phagocytose apoptotic cells. As hemocytes spread throughout the embryo, they synthesize extracellular matrix and peroxidasin, incorporating it into completed basement membranes. Cultured cells secrete peroxidasin; it occurs in larvae and adults. Each 1512 residue chain of the three-armed, disulfide-linked homotrimer combines a peroxidase domain with six leucine-rich regions, four Ig loops, a thrombospondin/procollagen homology and an amphipathic alpha-helix. The peroxidase domain is homologous with human myeloperoxidase and eosinophil peroxidase. This heme protein catalyzes H2O2-driven radioiodinations, oxidations and formation of dityrosine. We propose that peroxidasin functions uniquely in extracellular matrix consolidation, phagocytosis and defense.

Amino Acid Sequence↗

Tiggrin, a novel Drosophila extracellular matrix protein that functions as a ligand for Drosophila alpha PS2 beta PS integrins.

Genetic and other studies of Drosophila integrins have implicated these extracellular matrix receptors in various morphogenetic events, but identification of their endogenous ligands has been elusive. We report the biochemical purification and cloning of tiggrin, a novel extracellular matrix protein from Drosophila. This 255 x 10(3) M(r) polypeptide contains the potential integrin recognition sequence Arg-Gly-Asp (RGD) and 16 repeats of a novel 73-77 amino acid motif. The tiggrin gene is at chromosome locus 26D1-2 and is expressed by embryonic hemocytes and fat body cells. Tiggrin protein is detected in matrices, especially at muscle attachment sites that also strongly express integrins. Tiggrin-coated surfaces support primary embryo cell culture and provide excellent substrates for alpha PS2 beta PS integrin-mediated cell spreading. Soluble RGD-peptides inhibit this cell spreading.

Amino Acid Sequence↗

Venous stasis: successful outcome, and symptomatic relief in patients undergoing Linton procedures.

A retrospective study of forty-one patients who had undergone subfascial ligation of perforating veins in the lower extremity, or Linton procedure, is presented. All procedures were performed by the same surgeon from 1971 to 1993. Two patients underwent bilateral procedures. There were 28 female patients and 13 males. Fifteen had a history of smoking. There was a history of previous thrombophlebitis in 21 patients, and 21 had a family history of varicosities and/or ulceration. Results of venograms and Doppler duplex studies, if done, were evaluated. Follow up procedures, such as sclerosing injections and skin grafts, were also noted. A total of 25 patients had subsequent sclerosing injections, one underwent debridement twice, and one received skin grafts, secondary to incisional skin necrosis. It was noted that there was no occurrence of wound infection or incisional necrosis when zinc oxide paste boots were applied and maintained post-operatively. All patients were contacted directly prior to the writing of this article to ascertain prevalence, severity, and circumstances of recurrence.

Adult↗

Site-specific cleavage of basement membrane collagen IV during Drosophila metamorphosis.

Breakdown of basement membranes is an important step in the controlled rearrangement of cells during metamorphosis, cell migration, and metastatic spread of tumor cells. One of our two laboratories found a unique collagenous peptide that only appears during metamorphosis of Drosophila melanogaster. The other laboratory previously reported that during 20-hydroxyecdysone-induced eversion of Drosophila imaginal discs a glycoprotein named gp125 arises (Birr et al., 1990). We show that these two peptides are identical and that they are formed from basement membrane collagen IV. Cleavage occurs at an imperfection of this homotrimeric collagen helix between residues 755/756 in the sequence CALDE/IKMPAK. The peptide is the carboxyl fragment, 100,647 M(r), as derived from the amino acid sequence of the collagen alpha 1(IV) chain. The corresponding amino fragment was also recovered from a disulfide-linked aggregate. This specific cleavage supports the concept of highly targeted, controlled breakdown of basement membranes during metamorphosis. Furthermore, these cuts occur at strategic sites of the predicted supramolecular network of collagen IV molecules of Drosophila basement membranes.

Amino Acid Sequence↗

Effect of oxygenator type and bypass flow pattern on the P(a-ET)CO2 gradient.

Changes in pre-bypass and post-bypass P(a-ET)CO2 gradients were evaluated regarding the type of bypass flow (pulsatile or nonpulsatile) and oxygenator (membrane or bubble). Duration of bypass and hemodynamic changes were analyzed also to determine their possible influence on PaCO2, PETCO2, and P(a-ET)CO2. A total of 36 adult patients undergoing cardiopulmonary bypass were anesthetized using a sufentanil-pancuronium-oxygen technique. Patients were divided into three groups based on the type of oxygenator and pump flow: group 1 (control group) consisted of a bubble oxygenator with nonpulsatile flow (BN), group 2 consisted of a bubble oxygenator with pulsatile flow (BP), and group 3 consisted of a membrane oxygenator with nonpulsatile flow (MN). Cardiac parameters (MAP, CI, SVR, and PVR) PaCO2, PETCO2, and P(a-ET)CO2 were determined pre-bypass and post-bypass following steady-state conditions. For the entire group there was a trend for the P(a-ET)CO2 gradient to increase in the post-bypass period (pre-bypass = 3.5 +/- 0.5 mm Hg, post-bypass = 4.3 +/- 0.5 mm Hg.). However, this increase was not statistically significant. Pulsatile flow (group 2) demonstrated a significant correlation with the change in P(a-ET)CO2 gradients from the pre-bypass to the post-bypass period (r = 0.85) when compared with the other two groups (group 1: r = -0.09 and group 3: r = 0.37). Thus, the P(a-ET)CO2 gradient tended to remain constant from the pre-bypass to the post-bypass period in group 2, whereas it increased in groups 1 and 3. Changes in MAP, CI, SVR, and PVR and the duration of CPB did not influence the P(a-ET)CO2 gradient.

Adult↗

Acceptance testing of radiologic systems: experience in testing 129 imaging systems at two major medical facilities.

The problems encountered in acceptance testing of newly installed imaging equipment at two major medical institutions over a 10-year period are presented. Acceptance tests were conducted in 129 newly installed imaging systems with conventional acceptance testing methods. A total of 1,132 problems were documented. Problems were classified as major or minor; there were 772 major problems and 360 minor problems. An average of six major and three minor problems were documented in each new equipment installation tested. In some instances, final payment was withheld for several months or more to ensure correction of the problems identified. This experience confirms the need of thorough acceptance testing of new imaging equipment before final payment is made to the vendor.

Alabama↗

Industrial experience with the detection of retroviruses.

An important aspect of the virological assessment of cell substrates used to produce biologicals is their retroviral status. In this presentation we will attempt to document some of the practical experiences of industry when testing cell substrates for retroviruses using infectivity tests, reverse transcriptase and electron microscopy. We will also explore some important aspects of the experimental design of these retrovirus assay systems and review some results from the application of these methods in model, experimental systems.

Animals↗

Glutactin, a novel Drosophila basement membrane-related glycoprotein with sequence similarity to serine esterases.

Glutactin, a new acidic sulfated glycoprotein, was isolated from Drosophila Kc cell culture media. Immunofluorescence microscopy located it to embryonic basement membranes, particularly to the sequentially invaginated envelope of the central nervous system, muscle apodemes and dorsal median cell processes. Its chromosome locus is 29D. The nucleic acid sequence coding for the 1023 residue long polypeptide contains one intron and was confirmed by partial amino acid sequencing. Glutactin has a signal peptide and an amino domain of greater than 500 residues that strongly resembles acetylcholine esterases and other serine esterases, but lacks the catalytically critical serine residue. The amino and carboxyl domains of glutactin are separated by 13 contiguous threonine residues. Glutamine and glutamic acid make up 44% of glutactin's very acidic carboxyl domain. Glutactin preferentially binds Ca2+ in the presence of excess Mg2+ and four of its tyrosines are O-sulfated. Several similarities with mammalian entactin caused our previous, preliminary mention of glutactin as a putative Drosophila entactin, but sequence comparison now shows them to be different proteins.

Amino Acid Sequence↗

The developmentally disabled elderly: concerns of service providers.

We examined the availability of services for the developmentally disabled elderly and the concerns expressed by the service provider. We compared agencies which traditionally served individuals with developmental disabilities versus those serving the elderly populations. Although both types of agencies recognized the need for services, concern was raised as to who would provide them and how the two groups would blend.

Aged↗