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Biomedical subjects

D Walker

Publications and source records attributed to D Walker.

At least 451 records · Page 25Linked to original sources

Reference range and repeatability of a combined intestinal permeability and function test in clinically healthy Irish setter dogs.

A reference range was determined for a combined test of differential sugar permeability, using lactulose (L) and rhamnose (R), and intestinal function, using D-xylulose (X) and 3-O-methylglucose (G), in clinically healthy adult Irish setter dogs. Urinary L/R ratios in 48 Irish setters from one to 12 years old varied from 0.03 to 0.18, with a mean (SEM) of 0.10 (0.01); X/G ratios varied from 0.46 to 0.81, with a mean (SEM) of 0.59 (0.01). There were no significant differences between L/R or X/G ratios of dogs of different sex (P > 0.2) or age (P > 0.5), using analysis of covariance. Lactulose/rhamnose ratios of > or = 0.18 and X/G ratios > or = 0.43 were considered normal, defined by the respective mean +/- 2SD. Repeatability was established by performing three permeability and function tests at monthly intervals in twelve of the dogs. Analysis of repeated L/R and X/G ratios by means of linear models procedure revealed no significant differences between measurements made on successive occasions (P > 0.15), confirming the repeatability of this test.

Aging↗

Inflammation and Alzheimer's disease.

Inflammation clearly occurs in pathologically vulnerable regions of the Alzheimer's disease (AD) brain, and it does so with the full complexity of local peripheral inflammatory responses. In the periphery, degenerating tissue and the deposition of highly insoluble abnormal materials are classical stimulants of inflammation. Likewise, in the AD brain damaged neurons and neurites and highly insoluble amyloid beta peptide deposits and neurofibrillary tangles provide obvious stimuli for inflammation. Because these stimuli are discrete, microlocalized, and present from early preclinical to terminal stages of AD, local upregulation of complement, cytokines, acute phase reactants, and other inflammatory mediators is also discrete, microlocalized, and chronic. Cumulated over many years, direct and bystander damage from AD inflammatory mechanisms is likely to significantly exacerbate the very pathogenic processes that gave rise to it. Thus, animal models and clinical studies, although still in their infancy, strongly suggest that AD inflammation significantly contributes to AD pathogenesis. By better understanding AD inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approaches that may not cure AD but will likely help slow the progression or delay the onset of this devastating disorder.

Alzheimer Disease↗

Use of phthaloyl protecting group for the automated synthesis of 3'-[(hydroxypropyl)amino] and 3'-[(hydroxypropyl)triglycyl] oligonucleotide conjugates.

The chemical stability of oligonucleotides (ODNs) containing 3'-propanolamine was investigated. Invariably, all the ODNs synthesized from Fmoc-protected 3-aminopropane-1,2-diol-CPG support gave a mixture of three compounds at the end of automated synthesis as analyzed by denaturing PAGE and HPLC. On the basis of analytical procedures, these compounds were identified to be 3'-[N-acetyl-N-(hydroxypropyl)amino],3'-[(hydroxypropyl)amino], and 3'-hydroxyl ODNs. The instability of the amino protecting group under the synthesis conditions was responsible for this observed heterogeneity. In order to evaluate the stability, a comparative study on the chemical stability of the ODN containing amino-protecting groups such as [(9-fluorenylmethyl)oxy]carbonyl (Fmoc), trifluoroacetyl (TFA), and phthaloyl was undertaken. The results indicate that the phthaloyl group provided the best stability for the synthesis of 3' amine-modified ODNs, and the protecting group is cleaved and deprotected in concentrated ammonium hydroxide:40% aqueous methylamine, 1:1, for 5-10 min, at 56 degrees C. The 3'-hydroxypropyl)triglycyl] ODN conjugates were also synthesized from Fmoc- and phthaloyl-protected (hydroxypropyl)triglycine-CPG supports.

Base Sequence↗

One-lung versus two-lung ventilation in the closed-chest anesthetized dog: a comparison of cardiopulmonary parameters.

OBJECTIVE: To evaluate cardiopulmonary effects of one-lung ventilation (OLV) versus two-lung ventilation (TLV) in closed-chest anesthetized dogs. STUDY DESIGN: Controlled, randomized experiment. ANIMALS: Fourteen, 2- to 7-year-old adult dogs, weighing 23 +/- 6 kg. METHODS: The dogs were anesthetized with acepromazine, morphine, thiopental, and halothane in oxygen, ventilated, and paralyzed with vecuronium. Tidal volume was 10 mL/kg. Respiratory rate was set to maintain end-tidal CO2 (ETCO2) at 40 +/- 2 mm Hg before instrumentation then not changed. The left bronchus of 7 dogs was obstructed with a Univent bronchial blocker (Fuji Systems Corp, Tokyo, Japan). Blood gas analysis and hemodynamic measurements were taken at predetermined intervals for 1 hour in the TLV group and at baseline and following bronchial obstruction in the OLV group. RESULTS: Shunt fraction was not significantly different between groups, but in OLV shunt increased from baseline at 5 minutes. Arterial oxygen (PaO2) decreased after baseline in OLV compared with TLV. Arterial carbon dioxide (PaCO2) increased with OLV and decreased with TLV. In OLV, systemic vascular resistance was variable and decreased compared with TLV. Cardiac index increased over time in both groups but was not affected by treatment. Heart rate, mean arterial pressure, and diastolic arterial pressure increased with OLV compared with TLV but did not change over time. CONCLUSION: This study shows that OLV statistically decreases oxygen tension and transiently increases shunt fraction, but with 100% O2 it appears to be a feasible procedure with minimal cardiopulmonary side effects in healthy dogs. CLINICAL RELEVANCE: OLV is a feasible procedure in anesthetized dogs to better facilitate thoracic procedures such as bronchopleural fistula repair and thoracoscopy.

Anesthesia, General↗

Pharmacokinetic/pharmacodynamic assessment of the effects of E4031, cisapride, terfenadine and terodiline on monophasic action potential duration in dog.

1. Torsades de pointes (TDP) is a potentially fatal ventricular tachycardia associated with increases in QT interval and monophasic action potential duration (MAPD). TDP is a side-effect that has led to withdrawal of several drugs from the market (e.g. terfenadine and terodiline). 2. The potential of compounds to cause TDP was evaluated by monitoring their effects on MAPD in dog. Four compounds known to increase QT interval and cause TDP were investigated: terfenadine, terodiline, cisapride and E4031. On the basis that only free drug in the systemic circulation will elicit a pharmacological response target, free concentrations in plasma were selected to mimic the free drug exposures in man. Infusion regimens were designed that rapidly achieved and maintained target-free concentrations of these drugs in plasma and data on the relationship between free concentration and changes in MAPD were obtained for these compounds. 3. These data indicate that the free ED50 in plasma for terfenadine (1.9 nM), terodiline (76 nM), cisapride (11 nM) and E4031 (1.9 nM) closely correlate with the free concentration in man causing QT effects. For compounds that have shown TDP in the clinic (terfenadine, terodiline, cisapride) there is little differentiation between the dog ED50 and the efficacious free plasma concentrations in man (< 10-fold) reflecting their limited safety margins. These data underline the need to maximize the therapeutic ratio with respect to TDP in potential development candidates and the importance of using free drug concentrations in pharmacokinetic/pharmacodynamic studies.

Action Potentials↗

A COMIT model utilization to improve first-case start time.

The purpose of this article is to review the problems and processes impacting the deviation in first-case actual start times when compared to first-case scheduled start times. This article will also discuss the Continuous Outcomes Measurement and Improvement Technique (COMIT) model for problem resolution and share the experiences encountered by a group of collaborative nurse manager leaders in their outcome improvement efforts. The overall process improvements are discussed using the eight-step COMIT model, which showed the overall success of the project.

Analysis of Variance↗

Microvascular free tissue transfer: results in 57 consecutive cases.

OBJECTIVE: To evaluate the outcomes and complications in a consecutive series of animals undergoing microvascular reconstructive procedures at two veterinary institutions. STUDY DESIGN: Retrospective study. ANIMALS OR SAMPLE POPULATION: A total of 44 client-owned dogs and one red-necked wallaby. METHODS: The medical records of all animals undergoing reconstructive microsurgical procedures at the Western College of Veterinary Medicine and Michigan State University were reviewed. Microvascular flap survival and related complications were described. Statistical analysis was performed to determine the significance of relationships between operative factors and outcome. RESULTS: A total of 57 microvascular procedures were performed on 55 animals. Reconstruction was required after trauma in 42 animals, after ablative cancer surgery in 11 animals and for correction of congenital tissue aplasia in I animal. Donor tissues included the superficial cervical cutaneous, medial saphenous fasciocutaneous or musculofasciocutaneous, caudal superficial epigastric cutaneous, trapezius muscle or musculocutaneous, caudal sartorius muscle, latissimus dorsi muscle or musculocutaneous, cranial abdominal myoperitoneal, carpal footpad, digital footpad, and vascularized ulnar bone flaps. A total of 53 of 57 flaps (93%) survived. There was a significant relationship between flap failure and level of assistant surgeon experience (P < .05). Latissimus dorsi flaps were significantly more likely to fail when compared with pooled data from all other flap types (P < .01). CONCLUSIONS: The success of microvascular tissue transfer in this case series compares favorably with those reported in human reconstructive microsurgery. Both the primary and assistant surgeon should be practiced in microsurgical technique. Failure of latissimus dorsi flaps was not likely caused by an inherently deficient flap design, but was more likely attributed to the location and severity of trauma at the recipient site, the difficulty in isolating suitable recipient vessels for anastomosis or the absence of a trained assistant surgeon during these procedures. Clinical Relevance-This retrospective study documents the successful application of microvascular technique in a series of clinical cases requiring tissue reconstruction.

Anastomosis, Surgical↗

The response of contractile and non-contractile vacuoles of Paramecium calkinsi to widely varying salinities.

Paramecium calkinsi from tidal marshes survive a wide salinity range. Fluid output of contractile vacuoles of these cells decreased as salinity of the medium to which they were acclimated increased, and both pulse rate and vacuole volume were used to regulate output. When cells were first exposed to more dilute medium, contractile vacuoles greatly increased volume so that fluid output increased even though pulse rate decreased. In cells shifted to a more concentrated medium, contractile vacuole output decreased by decreasing pulse rate. The contractile vacuole is surrounded by a set of collecting structures which change form as the salinity changes. Distensible ampullae are found in media of low salinity and collecting canals are found in media of high salinity. When cells are shifted from high salinity to low, the number of ampullae increases and the number of canals decreases. When cells are shifted from low salinity to high, the number of ampullae decreases and the number of canals decreases. Other non-contracting vacuoles also appear in response to a hypoosmotic shock. These include vacuoles within the cell as well as "blisters" on the surface. The number and frequency of blisters increases with the size of the hypoosmotic shock. They detach from cells without resulting in any visible loss of cytoplasm. Non-contractile vacuoles may play a role in sequestering and removing excess water that the contractile vacuoles cannot handle.

Adaptation, Physiological↗

Calibration and use of an in-house anti-measles IgG standard serum.

For the purpose of research a large quantity of anti-measles IgG working reference serum was needed. A pool of sera from five teenagers was prepared and named Alexandre Herculano (AH). In order to calibrate the AH serum, 18 EIA assays were performed testing in parallel AH and the 2nd International Standard 1990, Anti-Measles Antibody, 66/202 (IS) in a range of dilutions (from 1/50 to 1/25,600). A method which compared parallel lines resulting from the graphic representation of the results of laboratory tests was used to estimate the power of AH relative to IS. A computer programme written by one of the authors was used to analyze the data and make potency estimates. Another method of analysis was used, comparing logistic curves relating serum concentrations with optical density by EIA. For that purpose an existing computer programme (WRANL) was used. The potency of AH relative to IS, by either method, was estimated to be 2.4. As IS has 5000 milli international units (mIU) of anti-measles IgG per millilitre (ml), we concluded that AH has 12,000 mIU/ml.

Adolescent↗

Phonocardiogram spectral analysis simulator of mitral valve prostheses.

Spectral analysis of sounds produced in vitro by mitral valve prostheses placed in a specially designed flow simulator has been carried out using a short-time Fourier representation of the recorded signal. Time variations of power spectra are displayed as a three-dimensional plot. Sounds produced by three types of valves, namely ball and cage, tilting disk and porcine valves, were analysed. Each valve type produced a characteristic spectrogram, and, for a given valve, spectrograms were reproducible to within a margin of 5 dB. The simulator may be used to detect structural deficiencies and functional abnormalities of prosthetic heart valves. In addition to quantifying the noise level of mechanical valves, the system may be used for quality control purposes to identify faulty valves.

Equipment Design↗

Kid's stuff.

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Child↗

Therapeutic computing: teaching therapeutic communications utilizing a videodisc.

Effective communication skills for nurses are essential and serve as the interface between patients and health care providers. Yet, teaching communication skills is subject to only limited success. Results vary according to the mix of students, the talent and interest of the instructor, and the availability of teaching time for the topic. The nursing program at Indiana University Kokomo is addressing the needs of nursing students with a multimedia computer system. A videodisc on therapeutic communication was purchased to supply the desired video-based examples. The programming of the computer interface was done by a senior information systems department major. Student attitudes measured after using the system the first year were very good.

Attitude↗

The Australian Medicines Handbook and its controlling vocabularies.

The Australian Medicines Handbook is intended to serve as an independent peer-reviewed knowledge resource for health care providers. A printed handbook is planned first, followed by electronic products. Information about medication will be dissected and entered into a detailed database, whose elemental nature should make it "computer understandable." The terms used in the database will be cross-referenced to preferred terms. Thus, the vocabulary will be controlled. The handbook will be printed directly from the database with use of database publishing techniques.

Australia↗