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 SNVDO has not been updated since 1977 and is outdated and inadequate to express the current state of medical knowledge.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.

Therapeutic information on the Internet.

The internet provides a vast array of information accessible to anyone with a personal computer, a modem, and an internet account. It can be difficult to locate appropriate sites and determine their utility. This article provides a point-in-time sampling of the internet for therapeutic information. The URL for sites are provided along with a brief review of the content and its applicability to veterinary therapeutics.

Pharmacokinetics of ketoprofen in healthy foals less than twenty-four hours old.

OBJECTIVE: To determine pharmacokinetic variables that describe disposition of ketoprofen after its i.v. administration to foals < 24 hours old. ANIMALS: 6 healthy foals (1 male and 5 females); mean age, 12.5 (range, 8.5 to 17) hours at time of dose administration. PROCEDURE: Ketoprofen was administered i.v. to foals at a dosage of 2.2 mg/kg of body weight. Ketoprofen concentration in plasma samples was analyzed, using high-performance liquid chromatography. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined times during a 48-hour period. Samples were centrifuged, and plasma was frozen at -70 C until analyzed. One-, two-, and three-compartment analyses were conducted. The most appropriate model was determined by use of Akaike's information criterion analysis. RESULTS: Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance (normalized for body weight) was significantly lower than that determined for adult horses. Volume of distribution (normalized for body weight) was larger than that determined for adult horses. Mean (harmonic) plasma half-life for healthy foals < 24 hours old was 4.3 hours. CLINICAL RELEVANCE: Although additional factors, such as dehydration or sepsis, must be considered on a case-by-case basis, the dose of ketoprofen administered to foals < 24 hours old should be different from the dose administered to adult horses. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to produce comparable therapeutic concentrations; longer dose intervals, based on clinical response, would be necessary to avoid drug toxicity.

Pharmacokinetics of flunixin meglumine in healthy foals less than twenty-four hours old.

OBJECTIVE: To determine pharmacokinetic variables that describe the disposition of flunixin after i.v. administration of flunixin meglumine to foals < 24 hours old. ANIMALS: 6 healthy foals, 2 males and 4 females (mean age, 11.6 hours; range, 6 to 22.5 hours). PROCEDURE: Flunixin (as flunixin meglumine) was administered to foals at a dosage of 1.1 mg/kg of body weight. Flunixin concentration in plasma samples was analyzed, using gas chromatography/mass spectroscopy. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined intervals over a 48-hour period. Samples were centrifuged, and plasma was frozen at -70 C until analyzed. One-, two-, and three-compartment analyses were conducted. The most appropriate model was determined by Akaike's information criterion analysis. RESULTS: Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance was significantly lower than that determined for older foals and adult horses. Volume of distribution was larger than that determined for adults. Mean plasma half-life for healthy foals < 24 hours old was 8.5 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Although additional factors (eg, dehydration or sepsis) must be considered on a case-by-case basis, flunixin meglumine should be administered differently to foals < 24 hours old, compared with adults. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to induce comparable therapeutic concentrations; longer dose intervals, on the basis of clinical response, would be necessary to avoid drug toxicity.

Pharmacokinetics of phenylbutazone in neonatal foals.

Single doses (2.2 mg/kg of body weight) of phenylbutazone (PBZ) were administered IV to 6 neonatal horses (5 to 17 hours old at time of dosing). Plasma concentrations of PBZ and its metabolite oxyphenbutazone were monitored serially for 120 hours after drug administration. Pharmacokinetic variables were calculated, using 1- and 2-compartment open models. Descriptive equations from the best model for each foal were then used to derive model-independent variables describing PBZ disposition. Median volume of distribution at steady-state was 0.274 L/kg (range, 0.190 to 0.401 L/kg). Median terminal half-life was 7.4 (6.4 to 22.1) hours, and median total plasma clearance of PBZ for foals in this study was 0.018 L/kg/h (range, 0.013 to 0.038 L/kg/h). Volume of distribution was larger, half-life was longer, and total clearance was lower, compared with similar values reported for administration of PBZ to adult horses.

Effects of a 44-day administration of phenobarbital on disposition of clorazepate in dogs.

The disposition of clorazepate, a benzodiazepine anticonvulsant, was determined in dogs after administration of a single oral dose of clorazepate (2 mg/kg of body weight) and after oral administration of clorazepate (2 mg/kg, q 12 h) concurrently with phenobarbital (5 mg/kg, q 12 h) for 44 consecutive days. Serum concentrations of nordiazepam, the active metabolite of clorazepate, were measured. After a single oral dose of clorazepate, maximal nordiazepam concentrations ranged from 569.6 to 1,387.9 ng/ml (mean, 880.2 +/- 248.9 ng/ml) and were detected 16.8 to 131.4 minutes (mean, 85.2 +/- 36 minutes) after dosing. After administration of phenobarbital for 44 consecutive days, maximal nordiazepam concentrations were significantly (P < 0.01) lower, ranging from 209.6 to 698.5 ng/ml (mean, 399.3 +/- 155.6 ng/ml) at 68.4 to 145.8 minutes (mean, 93 +/- 25.8 minutes) after dosing. Mean area under the curve (AUC) on day 1 (mean, 3.37 +/- 0.598 ng.min/ml) was significantly (P < 0.001) greater than AUC on day 44 (1.66 +/- 0.308 ng.min/ml). Oral clearance was significantly (P < 0.01) greater on day 44 (12.44 +/- 2.55 ml/min/kg), compared with that on day 1 (6.16 +/- 1.35 ml/min/kg). Values for area under the first moment curve, oral volume of distribution, mean residence time, and elimination half-life were not significantly altered by concurrent administration of phenobarbital. Administration of phenobarbital altered the disposition of clorazepate such that the amount of nordiazepam in circulation during each dose interval was significantly reduced. Adequate control of seizures in epileptic dogs, therefore, may require higher dosages of clorazepate when it is coadministered with phenobarbital.

Pharmacokinetic disposition of intravenous and oral pentoxifylline in horses.

The pharmacokinetics of pentoxifylline (P) and its alcohol metabolite I (MI) were determined after administration of intravenous pentoxifylline, sustained release pentoxifylline tablets (Trental), and crushed pentoxifylline tablets in corn syrup, to five healthy adult horses. Pharmacokinetics were evaluated in a model-independent manner. After intravenous administration, pentoxifylline was rapidly eliminated (mean residence time 1.09 +/- 0.67 h), had a large steady-state volume of distribution (2.81 +/- 1.16 l/kg), and high clearance (3.06 +/- 1.05 l/kg/h). Oral absorption of pentoxifylline from both dose forms varied considerably between individuals. Times to peak concentration ranged from 1-10 h for either dose form. There was no difference in relative bioavailability (F') between whole (0.98 +/- 0.30) and crushed Trental tablets. Ratios between areas under the curve (AUC) for pentoxifylline and MI were different following administration of oral versus intravenous doses. This finding suggests that route of administration may affect the metabolic profile of pentoxifylline. Given the extreme differences in absorption characteristics between individuals in this study, recommendations are not made as to appropriate dose, dose interval, or dose form for administration of pentoxifylline to horses.

Response to gonadotrophin-releasing hormone by the intact male dog: serum testosterone, luteinizing hormone and follicle-stimulating hormone.

In Expt 1, gonadotropin-releasing hormone (GnRH) (Cystorelin, CEVA) was administered intramuscularly to two intact male dogs; one dog received one injection of 50 micrograms GnRH and one dog received four daily injections of 50 micrograms GnRH. Both dogs exhibited a significant and immediate rise in luteinizing hormone (LH) following GnRH administration, with a peak observed at 15 min following injection. Testosterone was increased over baseline concentrations for 5 and 7 days, respectively, after the injection. In Expt 2, eight intact male dogs were injected intramuscularly with 0.7 microgram GnRH (Factrel, Fort Dodge) kg-1. Baseline testosterone concentrations were established by daily sampling for 14 days before treatment. All dogs exhibited an LH peak 15 min and a testosterone peak 60 min after the GnRH injection. Testosterone concentrations had returned to baseline concentrations by 4 h after the injection. Testosterone tended to fall below baseline concentrations for several days following the injection of GnRH. No peak was noted for follicle-stimulating hormone. In Expt 3, five additional dogs were injected with 0.7 microgram GnRH (Factrel, Fort Dodge) kg-1. Testosterone concentrations rose in all dogs 1 h after the injection and returned to baseline concentrations by 24 h after injection. In the male dog, GnRH stimulated an LH peak 15 min and a testosterone peak 1 h after injection. Further investigations are needed to elucidate the different effects on testosterone concentration observed with two different GnRH preparations.

Clinical pharmacology of antimicrobial drugs for the treatment of septic neonatal calves.

For a given infection, each antibiotic will have a probability of producing a beneficial outcome. Decisions that increase the antibacterial activity of the therapeutic regimen against the bacterial infection will increase the probability of a beneficial outcome. Unfortunately, such decisions may increase the cost of therapy or the risks of toxicity. Finally, neonatal calves presented for therapy are not of uniform value. It is logical to employ different antimicrobial drugs and ancillary therapies when the value of the individual calf is considered. A constructive balance between efficacy, cost, and toxicity establishes the value of a therapeutic approach for the client.

Therapeutic decisions. Choosing appropriate antimicrobial therapy.

Certain principles and clinical techniques can be applied to antimicrobial therapy, whatever the specific circumstances. This review is intended to consider these general principles in the context of the decisions that must be made in order to apply antimicrobial therapy in veterinary patients. Attention is given to beneficial properties that contribute to action against bacterial infections, in both qualitative and quantitative terms. Selection of an antimicrobial is considered from the perspective of the laboratory test that can be used to support decisions. Finally, a structured and formal method for evaluating the overall decision making process is described.

Use of antimicrobial drugs to prevent infections in veterinary patients.

The usefulness of antimicrobial drugs for prevention of certain infections has been well proven. The use of antibiotics during surgery, in order to prevent increased morbidity and expense associated with surgical infections, is a well accepted part of clinical practice. Experience with various techniques for their administration suggests that refinement in drug selection, dosage, and the timing of administration improves the efficacy of prophylactic antimicrobials. For surgical implants, nontraditional uses of antimicrobial drugs are probably indicated. Urinary tract infections can be postponed beyond the need for continued catheterization in certain patients by judicious application of antimicrobials. The purpose of this review is to summarize the accepted principles of antimicrobial prophylaxis and to examine specific therapeutic regimens used for the prevention of infections in surgical patients, those requiring chronic urinary catheterization, dental patients, and severely ill and immunocompromised patients.

Drug residues in food animals.

A total of 292 field investigative reports of drug residues in food animals for 1983 to 1988 were analyzed. The investigations had been conducted by the Food and Drug Administration (FDA) and the Virginia State Veterinarian's Office, in cooperation with the Center for Veterinary Medicine of the FDA, to trace residues reported by the USDA Food Safety and Inspection Service to the source of the animal and the administration of the drug. The analysis disclosed the following. (1) Antibiotic residues were most often associated with streptomycin, penicillin, oxytetracycline, and neomycin. Sulfamethazine was, by far, the most frequently cited sulfonamide. (2) Residues are being found predominantly in cows, veal calves, and market hogs (barrows and gilts). (3) The cause of drug residue most frequently cited by the field investigators was failure to observe the withholding time for the drug. Almost half of these investigations revealed that the individual responsible for the sale of the animal did not know the proper withholding time for the drug. Failure to maintain adequate records was also a contributing factor. (4) The producer was considered to be the responsible party in over 80% of the cases for which responsibility was determined. (5) Residues associated with injectable drugs were investigated most frequently. Long-acting and sustained-release products were most often associated with penicillin and oxytetracycline residues. (6) The 2 most common sources of purchase for the drugs involved in the investigations were the feed/farm supply store and the veterinarian. (7) Unapproved drug use was not a major cause of residues.

Otopharmacology.

Therapy for diseases of the ear canal is, in most respects, similar to therapy for other diseases of dogs and cats. As a target for drug therapy, however, the unique anatomy of the external ear canal presents differences that are both advantageous and disadvantageous. This article will describe principles of therapy and pharmacologic properties from the perspective of topical therapy directed at the surface of the ear canal, the epidermis, and the dermis.

Suppurative colitis in a cat.

A young cat with chronic large bowel diarrhea was found to have suppurative colitis. Treatment with sulfasalazine resulted in prompt clinical improvement, although histologic abnormalities persisted. Three months later, the cat was euthanatized because of effusive feline infectious peritonitis. Histologic examination revealed a normal colon.

Determination of lidocaine concentrations producing therapeutic and toxic effects in dogs.

Lidocaine was infused at a fixed zero-order rate to eight healthy mongrel dogs until tonic extension (n = 5) and cortical seizures (n = 7) were produced. Lidocaine concentrations determined at 5-min intervals were used to calculate concentrations at which these effects occurred. The tonic extension phase occurred at a mean lidocaine concentration of 8.21 +/- 1.69 micrograms/ml. After a 1-month rest period, the same dogs were anaesthetized and ventricular tachycardia was produced by administering ouabain. Lidocaine was again infused at a fixed zero-order rate until all beats of ventricular origin were abolished. This occurred at a mean lidocaine concentration of 6.25 +/- 1.49 micrograms/ml.

Pharmacokinetics of digoxin in cattle.

Digoxin was administered as a single intravenous injection of 22 micrograms/kg to six cattle. The resulting serum concentrations were fitted by both a bi- and tri-exponential equation with the latter providing the best fit to the data of a majority of the animals. The biological half-life of digoxin in cattle was found to be 7.8 h. This relatively short half-life in comparison to other animal species dictates that digoxin should be administered more frequently to cattle to provide therapeutic concentrations in serum without broad fluctuations in serum concentrations. Computer simulations of various intravenous dosage regimens suggested that a loading dose of 22 micrograms/kg followed by an infusion of 0.86 micrograms/kg/h would offer the greatest safety and efficacy in bovine patients.

Pharmacokinetics of lidocaine and its active metabolites in dogs.

The pharmacokinetics of lidocaine in dogs were investigated following the intravenous and intramuscular administration of single doses of lidocaine hydrochloride. The mean elimination rate constant and the mean specific clearance determined for the intravenous portion of the study were 0.786 h-1 and 2.40 1/kg/h, respectively. Following intramuscular administration the mean absorption rate constant was 7.74 h-1. Absorption was nearly complete as the percentage of an intramuscular dose absorbed averaged 91.9%. Concentrations of two N-deethylated metabolites, determined following the administration of lidocaine suggest that monoethylglycinexylidide is eliminated rapidly while glycinexylidide is more slowly eliminated. The relative contribution of these metabolites to the therapeutic and toxic effects of lidocaine and the potential for glycinexylidide accumulation during lidocaine administration remain to be investigated.