Salvaging legacy data: mapping an obsolete medical nomenclature to a modern one.

The Veterinary Medical Database (VMDB) is a repository containing abstracts of over six million case records from 24 veterinary colleges throughout the U.S. and Canada. These case record abstracts, spanning almost 40 years, represent a valuable resource for outcomes analysis and hypothesis generation. Database records are currently encoded using the Standard Nomenclature of Veterinary Diseases and Operations (SNVDO), a precoordinated, hierarchical coding system. SNVDO has not been updated since 1977 and is outdated and inadequate to express the current state of medical knowledge. We undertook to manually map a subset of the SNVDO codes to a modern medical nomenclature, SNOMED-RT (Version 1.0), and to evaluate the quality of the resultant mappings and the acceptability of the mapping method used. We found that the distribution of frequency of use of the SNVDO codes in the VMDB records is highly skewed, with a small number of codes accounting for a large percentage of the records. We targeted our mapping efforts on that subset of codes. We found that our targeted manual mapping of the SNVDO codes to SNOMED-RT codes was feasible and produced good quality results, based on separate evaluations performed by two domain experts. However, a significant proportion of the SNVDO codes could not be mapped to a single SNOMED-RT concept, necessitating construction of multiple-code post-coordinated terms. Additionally, this manual mapping was very labor-intensive.

Developing a controlled vocabulary for use in a hospital information system.

In bringing a controlled vocabulary to a health information system, it is important to include those terms commonly used by those who must routinely input data to the system. We have developed a methodology whereby we can obtain "free text" descriptions of diagnoses entered by system users. We then sort those terms/concepts by system and find the appropriate "atomic" term(s). The terms are also being submitted to domain experts for appropriateness and fidelity. These concepts are then coded in an international coding system (SNOMED International) to eventually be entered into the controlled "pick list" of terms available for users to enter.

Virtual shelves. II: A unified catalog for a heterogeneous collection.

We describe a unified catalog of traditional and digital resources in medical informatics, using standard cataloging principles (AACR2), schemes (LCC), and coding formats (USMARC). The unified catalog integrates the bibliographic records of physical items in the heterogeneous collection with the bibliographic records of network accessible digital items, using prescribed cataloging formats to new effect. The unified catalog is collections-based. We do not use the MARC 856 field to specify the network location of a digital item. The location of a digital item is determined by mapping its call number through a location guide to a network address. This mapping is strictly isomorphic to the way the shelf location of a physical item is determined within the bounds of a controlled collection.

Delivery of laboratory data with World Wide Web technology.

We have developed an experimental World Wide Web (WWW) based system to deliver laboratory results to clinicians in our Veterinary Medical Teaching Hospital. Laboratory results are generated by the clinical pathology section of our Veterinary Medical Diagnostic Laboratory and stored in a legacy information system. This system does not interface directly to the hospital information system, and it cannot be accessed directly by clinicians. Our "meta" system first parses routine print reports and then instantiates the data into a modern, open-architecture relational database using a data model constructed with currently accepted international standards for data representation and communication. The system does not affect either of the existing legacy systems. Location-independent delivery of patient data is via a secure WWW based system which maximizes usability and allows "value-added" graphic representations. The data can be viewed with any web browser. Future extensibility and intra- and inter-institutional compatibility served as key design criteria. The system is in the process of being evaluated using accepted methods of assessment of information technologies.

Induction of early-phase endotoxin tolerance in horses.

Six, clinically healthy horses, of mixed age and sex, were infused via a jugular venous catheter with 100 ml of pyrogenfree sterile saline (PFSS; 0.9% NaCl). Animals were infused with Escherichia coli O55:B5 endotoxin (total dose = 50 ng/kg bwt), 24 (LPS-1) and 48 h (LPS-2) after PFSS infusion. Blood was collected before, and every 15 min after, each infusion for the first 8 h and then every 2 h for the following 14 h. Clinical responses (rectal temperature, heart rate, respiration rate and blood pressure) were determined before and every 4 h after each infusion for 20 h. Geometric mean anti-endotoxin antibody titres in serum samples, harvested just before each infusion, were unchanged over the course of the experiment. Serum tumour necrosis factor-alpha (TNF alpha) activity was estimated using a cytotoxic bioassay and WEHI 164 clone 13 murine fibrosarcoma cells as targets. Mean clinical parameter values and geometric mean serum TNF alpha activity at given time points were compared across the 3 infusions. Both LPS-1 and LPS-2 resulted in elevated mean rectal temperature at 4 h after infusion. However, duration of mean rectal temperature elevation was greater (P < 0.05) after LPS-1 (through 12 h) than after LPS-2 (through 8 h). More substantial increases in systolic and diastolic blood pressure were observed after LPS-1 than LPS-2 and mean systolic blood pressure after LPS-1 was elevated at 4 h when compared to PFSS (P < 0.05). Decreased systolic and diastolic blood pressures were observed at 16 h after both LPS infusions, when compared to PFSS infusion. Heart rate was increased, compared to PFSS, after both LPS-1 (8-12 h) and LPS-2 (4-12 h) (P < 0.05). No significant elevations in mean respiratory rate were observed after either LPS-1 or LPS-2 when compared to PFSS. However, at 4 h post infusion, mean respiratory rate after LPS-2 was greater (P < 0.05) than that after LPS-1. Serum TNF alpha activity was not detected after infusion of PFSS, but was detected after both LPS-1 and LPS-2. Serum TNF alpha activity was elevated earlier, was present in higher concentrations and persisted longer after LPS-1 than after LPS-2 (P < 0.05). The decreased duration of fever and attenuated serum TNF alpha response subsequent to successive sublethal LPS challenge observed in this study support the conclusion that these horses developed early-phase endotoxin tolerance (EPET) and, therefore, contributes to the understanding of the role of endotoxaemia in a number of clinical conditions in horses.

World Wide Web-based access to heterogenous information resources for cytokine research and education.

Cytokines are currently the focus of intense research efforts, and information related to cytokine biology is expanding at an extremely rapid rate. The primary literature has become insufficient as a source for timely information, and efficient searches of the older literature are complicated by the nature of cytokine nomenclature. A few computer-accessible cytokine-related data sources have recently been developed, but these are typically limited in scope and not integrated with other information resources. We have developed Cytokine Explorer, a World Wide Web (WWW)-based resource to provide access to and guidance in use of information for research and education in cytokine biology. The resource consists of: (1) a searchable thesaurus of cytokine nomenclature; (2) a cytokine reagent database containing information from academic institutions and commercial sources; (3) a set of links to cytokine-related WWW sites; and (4) a database of functional information retrieval maps for guided retrieval of cytokine information from combinations of heterogeneous sources.

Quantitation of bovine TNF-alpha mRNA by reverse transcription and competitive polymerase chain reaction amplification.

A reverse transcription (RT) and competitive polymerase chain reaction (PCR) amplification technique was developed to quantify bovine tumor necrosis factor-alpha (TNF-alpha) mRNA. A bovine TNF-alpha cDNA insert containing plasmid was used to produce a 237-bp cDNA competitive template which, when PCR-amplified with primers designed to amplify bovine TNF-alpha cDNA, resulted in a 147-bp product distinguishable by agarose gel electrophoresis from the 378-bp TNF-alpha RT-PCR-amplified cDNA product. Dilutions of competitive template were co-amplified with constant amounts of total cellular RNA harvested from bovine alveolar macrophages (BAM). Products were separated in ethidium-bromide-stained agarose gels and relative amounts of TNF-alpha mRNA were determined by densitometric scanning of TNF-alpha cDNA and competitive template product bands on photographic negatives. Digestions with Pvu II and Sty I restriction endonucleases verified that RT-PCR-amplified TNF-alpha cDNA products were authentic. A time study indicated that TNF-alpha mRNA concentrations peaked 3 h after endotoxin and virus induction of BAMs.

IFN-gamma stimulates IgG2 production from bovine B cells costimulated with anti-mu and mitogen.

The effect of interferon-gamma (IFN-gamma) antibody production by anti-mu- or pokeweed mitogen-stimulated bovine B cells was studied. IFN-gamma induced IgG2 secretion in isolated bulk B cell populations and in B cells sorted for IgM expression. IgM production was suppressed by the presence of IFN-gamma alone but this effect was antagonized by interleukin 2 (IL2). The effects of IFN-gamma on secreted levels of IgM, IgG1, and IgG2 correlated with the frequencies of cells expressing transcripts of the respective isotypes when stimulated with IFN-gamma-containing T cell supernatants. These results indicate that IFN-gamma plays a key role in IgG2 production in the bovine by directly affecting suitably stimulated B cells. The ability of IL2 to synergize with IFN-gamma to augment both the IgM and IgG2 responses implicates a TH1-like subset in regulation of this isotype.

Use of random amplified polymorphic DNA analysis to compare Babesia bovis and B. bigemina isolates.

Random amplified polymorphic DNA analysis provides characteristic fingerprints for Babesia bovis and B. bigemina. This genetic profile reflects similarities and minor differences between closely related regional isolates and the greater diversity representative of species from distant geographic locations.

Fluorescence-activated cell sorting-derived clones of Babesia bigemina show karyotype polymorphism.

Use of the fluorescence-activated cell sorter proved to be an accurate and highly efficient means for cloning Babesia parasites. These qualities were examined by separating a mixed population of Babesia-infected bovine erythrocytes composed of two isolates with different karyotypes. Direct evidence of polymorphism was detected during comparison of the resultant clones.

Serum tumor necrosis factor alpha concentrations and clinical abnormalities in colostrum-fed and colostrum-deprived neonatal foals given endotoxin.

We examined the effect of infusion of lipopolysaccharide (LPS) on serum tumor necrosis factor alpha (TNF alpha) concentration and clinical attitude in 2- 3-day-old colostrum-fed (CF) and colostrum-deprived (CD) foals. Eleven CF and 8 CD neonatal foals were given a bolus i.v. infusion of Escherichia coli O55:B5 lipopolysaccharide (0.5 microgram/kg of body weight) in sterile saline (0.9% NaCl) solution. Four CF and 2 CD foals were given saline solution alone. Serum IgG concentration and serum anti-LPS IgG(T) antibody titer were determined for each foal prior to infusion. A depression index was used to score clinical abnormalities. Serum TNF alpha concentration was estimated by use of an in vitro cytotoxicity bioassay that used WEHI 164 clone 13 cells as targets. The cytotoxic serum factor was identified as TNF alpha by immunoprecipitation with caprine antisera raised against the 15 NH2-terminal amino acids of human TNF alpha. Tumor necrosis factor alpha was not detected in any preinfusion serum samples nor in any samples from foals given saline solution alone. Serum TNF alpha concentration increased in all LPS-infused foals and peaked between 60 and 90 minutes after infusion. Serum TNF alpha concentrations, expressed as mean percentage of peak serum TNF alpha concentration, persisted longer in CD foals given LPS than in CF foals given LPS. All LPS-infused foals displayed clinical signs of endotoxemia, but mean depression index scores of the CF and CD foals given LPS were not significantly different at any time. Serum TNF alpha concentrations were correlated with depression index scores in both LPS-infused groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum interleukin-6 concentrations in endotoxin-infused neonatal foals.

Serum interleukin-6 (IL-6) concentration was measured in 11 colostrum-fed (CF) and 8 colostrum-deprived (CD) 2- to 3-day-old foals after foals were infused with lipopolysaccharide (LPS; Escherichia coli O55:B5 endotoxin, 0.5 microgram/kg of body weight in sterile saline [0.9% NaCl] solution). Four CF and 2 CD foals were given saline solution alone. Serum IL-6 concentration was estimated by use of an in vitro proliferative bioassay, using the IL-6 dependent B.13.29 clone 9 cells. Interleukin-6 concentration increased in all LPS-infused foals, and geometric mean serum IL-6 concentration was significantly higher in CF than CD foals 30 and 90 minutes after infusion. Both LPS-infused groups had multiple spikes of mean IL-6 concentration that peaked at 120 minutes in CF foals and 150 minutes in CD foals. Results indicated that IL-6 is produced in neonatal foals in response to LPS infusion. Furthermore, colostrum deprivation resulted in longer times to peak mean serum IL-6 concentration and tended to reduce serum IL-6 concentration in neonatal foals.

A prospective study of septicaemia in colostrum-deprived foals.

Fourteen mares and their foals were attended at parturition. After mare-foal bonding, 8 colostrum-deprived (CD) foals were removed from their dams, deprived of colostrum, and provided with an alternative milk source for the first 24 h of life. The mares were milked out every 2-4 h during this period to remove colostrum, after which the CD foals were returned to their mares and allowed to nurse. Six colostrum-fed (CF) foals were allowed to suck colostrum in the normal manner. Foal serum IgG concentration was determined by single radial immunodiffusion (means, CD = 0 mg/dl; CF = 1,508 mg/dl). Accepted methods were used to minimise infections in the neonatal foals. Of the 8 CD foals, 7 demonstrated clinical signs of sepsis. Septicaemia was confirmed in 5 of the 7 septicaemic CD foals by ante-mortem blood culture or by culture of tissue at necropsy. Organisms isolated included: Actinobacillus equuli, Escherichia coli, undifferentiated coliforms, Pseudomonas spp., and Actinomyces pyogenes. Clinically ill foals were treated with antimicrobial drugs, intravenous fluid therapy, flunixin meglumine, and anti-endotoxin hyperimmune serum. Three septicaemic CD foals survived. Four of 7 septicaemic CD foals died or were destroyed. Post-mortem lesions included bacterial embolic pneumonia, glomerulonephritis/nephritis, lymphoid depletion/atrophy, splenic and lymphoid necrosis, hepatitis, septic arthritis, and systemic bacterial embolism. None of the CF foals became septicaemic. One CF foal had foal heat diarrhoea and 1 CF foal had a serum IgG concentration of 160 mg/dl (i.e. failure of passive transfer), but both foals were otherwise normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption of an alternate source of immunoglobulin in pups.

Newborn pups from 4 large litters were alloted to 6 groups to determine effect of time and route of administration on absorption of an alternate source of immunoglobulin. Selective absorption of specific classes of immunoglobulins was also investigated. The alternate source of immunoglobulin consisted of pooled serum that was administered either PO or SC. Control groups were either left with the dam (group C1) or fed milk replacer (group C2). Blood samples were collected from pups at birth and 24 hours. Immunoglobulin (IgA, IgG, IgM) concentrations were determined by use of radial immunodiffusion on samples of pooled serum, colostrum, and pups' serum (birth and 24 hours). Serum IgA concentration was less than the sensitivity of the procedure and was not included in the statistical analysis. Pups fed 8 ml of pooled serum at birth and 12 hours later (group T1) absorbed more (P less than 0.05) IgG and IgM than did group-C2 pups, but less (P less than 0.05) than did group-C1 pups. Pups fed 8 ml of pooled serum at 12 hours only had significant (P less than 0.05) increase of IgG concentration, but no absorption of IgM (P greater than 0.05) at 24 hours, compared with control pups (group C2). Pups administered 8 ml of pooled serum SC at birth (group SC1) had similar (P greater than 0.05) absorption of IgG and higher (P less than 0.05) absorption of IgM than did pups of group T1.(ABSTRACT TRUNCATED AT 250 WORDS)

Release of tumor necrosis factor-alpha from bovine alveolar macrophages stimulated with bovine respiratory viruses and bacterial endotoxins.

The release of tumor necrosis factor-alpha (TNF-alpha) from cultured bovine alveolar macrophages (BAM) was evaluated following stimulation of BAM with bovine herpesvirus-1 (BHV-1), parainfluenza-3 (PI-3) virus, bovine respiratory syncytial virus (BRSV), Escherichia coli 0111:B4 endotoxin, Pasteurella haemolytica type 1 endotoxin, Pasteurella multocida endotoxin, and virus/endotoxin combinations. A cytotoxic assay system using Georgia bovine kidney cells as targets was used to measure TNF-alpha activity. The cytotoxic activity was neutralized by an anti-human TNF-alpha monoclonal antibody. Stimulation of BAM with 1 median tissue culture infectious dose (TCID50) of live or ultraviolet (UV)-inactivated PI-3 virus/cell resulted in release of TNF-alpha in significantly (P less than 0.05) higher amounts than sham-induced BAM. The quantities of TNF-alpha released after live or UV-inactivated BHV-1 or BRSV induction were not significantly higher than sham-induced BAM. E. coli 0111:B4, P. haemolytica type 1 and P. multocida endotoxins stimulated TNF-alpha release in a dose-dependent manner. Sequential exposure of BAM to 1 TCID50 per cell of either live BHV-1, PI-3 virus or BRSV and then 5 micrograms ml-1 of either E. coli 0111:B4, P. haemolytica type 1 or P. multocida endotoxin caused a significant (P less than 0.05) reduction in detectable TNF-alpha in seven of nine virus/endotoxin combinations tested, when compared with 5 micrograms ml-1 of endotoxin alone. Parainfluenza-3 virus/endotoxin combinations stimulated higher TNF-alpha release when compared with other virus/endotoxin combinations. Five out of six test animals had serum-neutralizing antibodies to PI-3 virus, one out of six had serum-neutralizing antibodies to BHV-1, and two out of six had serum-neutralizing antibodies to BRSV, suggesting a possible relationship between serum neutralizing antibodies and TNF-alpha release from in vitro cultivated BAM.

Effect of bovine fibroblast interferon on rhinovirus infection in calves.

The prophylactic/therapeutic activity of natural bovine fibroblast interferon (BoF-IFN) against bovine rhinovirus infection in calves was assessed. Six calves were each given 8 intranasal inoculations of partially purified BoF-IFN (3.25 x 10(5) U at 8 AM, 11 AM, 5 PM, and 8PM on day 1 and 8 AM, 11 AM, 2 PM, and 5PM on day 2), and 6 calves were given placebo. All calves were challenge exposed with 10(5.1) TCID50 of bovine rhinovirus after the first 2 treatments (6 hours after the first IFN or placebo treatment). Nasal excretion of rhinovirus, IFN concentration in the nasal secretions, and nasal secretion and serum rhinovirus antibodies were measured before and at selected times after calves were inoculated. Interferon-treated calves excreted rhinovirus in their nasal secretions in lesser amounts (mean value, 0.84 log10 TCID50/ml vs 1.58 log10 TCID50/ml on postchallenge exposure days 1 and 2; (P less than 0.05) and for a shorter duration (P less than 0.05) than did placebo-treated calves. No calves developed clinical signs of respiratory tract illness. Rhinovirus antibody titer was not significantly different between IFN- and placebo-treated calves.

Partial purification and characterization of bovine fibroblast interferon.

Bovine fibroblast interferon (BoF-IFN), produced in primary bovine embryonic kidney cell cultures after priming and infection with bluetongue virus, was purified by controlled pore glass (CPG) chromatography to a specific activity of 10(6) U/mg of protein, with 40% recovery of the original activity. The crude IFN was concentrated more than sevenfold during purification. This proved to be a relatively simple, practical method of obtaining sufficient quantities of partially purified natural BoF-IFN for further studies. The CPG-purified BoF-IFN was further concentrated by sequential ultrafiltration and was analyzed by sodium dodecyl sulfate/polyacrylamide-gel electrophoresis (SDS-PAGE). Interferon, recovered from denaturing conditions either by dialysis against phosphate-buffered saline solution or by dilution in cell culture medium containing 10% fetal bovine serum, migrated as a single stainable protein with molecular weight of 21,000 on analytic SDS-PAGE gels. Recovered IFN activity from preparative SDS-PAGE totalled 8.7% of that applied. Attempts to further purify CPG-purified BoF-IFN by zinc chelate affinity chromatography were unsuccessful.

Beaded agarose affinity chromatography of bovine fibroblast interferon.

Bovine fibroblast interferon (BoF-IFN), produced in bovine embryonic kidney cell cultures by priming and infection with bluetongue virus, was partially purified by controlled pore glass chromatography. The partially purified BoF-IFN then was subjected to beaded agarose affinity chromatography in 2 distinct fractions--1 after the addition of 1M NaCl and the other one after the addition of 1.5M NaCl containing 50% ethylene glycol. Analysis of fractions by sodium dodecyl sulfate/polyacrylamide-gel electrophoresis revealed a broad molecular weight range (14,900 to 27,900) for IFN eluted by 1M NaCl, and 2 discrete molecular weight ranges (16,000 to 19,500 and 28,300 to 34,000) for IFN eluted by 1.5M NaCl containing 50% ethylene glycol. The specific activity of the IFN eluted with 1.5M NaCl containing ethylene glycol was 2.85 X 10(6) U/mg of protein, compared with 5.7 X 10(5) U/mg of protein in the controlled pore glass-purified IFN.