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Machine-learning methods can assist with the medical decision-making processes at the both the clinical and diagnostic levels. In this article, we first review historical milestones and specific applications of computer-based medical decision support tools in both veterinary and human medicine. Next, we take a mechanistic look at 3 archetypal learning algorithms—naive Bayes, decision trees, and neural network—commonly used to power these medical decision support tools. Last, we focus our discussion on the data sets used to train these algorithms and examine methods for validation, data representation, transformation, and feature selection. From this review, the reader should gain some appreciation for how these decision support tools have and can be used in medicine along with insight on their inner workings.

OBJECTIVE To test the hypothesis that once-daily oral administration of atenolol would attenuate the heart rate response to isoproterenol for 24 hours. ANIMALS 20 healthy dogs. PROCEDURES A double-blind randomized placebo-controlled crossover study was conducted. Dogs were assigned to receive atenolol (1 mg/kg, PO, q 24 h) or a placebo for 5 to 7 days. After a washout period of 7 days, dogs then received the other treatment. Heart rate at rest (HRr) and heart rate induced by administration of isoproterenol (HRi) as a constant rate infusion (0.2 μg/kg/min for 5 to 7 minutes) were obtained by use of ECG 0, 0.25, 3, 6, 12, 18, and 24 hours after administration of the final dose of atenolol or the placebo. A mixed-model ANOVA was used to evaluate effects of treatment, time after drug or placebo administration, treatment-by-time interaction, period, and sequence on HRr and HRi. RESULTS Effects of sequence or period were not detected. There was a significant effect of treatment and the treatment-by-time interaction on HRi. Atenolol significantly attenuated HRi for 24 hours but did so maximally at 3 hours (least squares mean ± SE, 146 ± 5 beats/min and 208 ± 5 beats/min for atenolol and placebo, respectively). The effect at 24 hours was small (193 ± 5 beats/min and 206 ± 5 beats/min for atenolol and placebo, respectively). Atenolol had a small but significant effect on HRr. CONCLUSIONS AND CLINICAL RELEVANCE This study of healthy dogs receiving atenolol supported a recommendation for a dosing interval < 24 hours.

Inflammatory bowel disease (IBD) and alimentary lymphoma (ALA) are common gastrointestinal diseases in cats. The very similar clinical signs and histopathologic features of these diseases make the distinction between them diagnostically challenging. We tested the use of supervised machine-learning algorithms to differentiate between the 2 diseases using data generated from noninvasive diagnostic tests. Three prediction models were developed using 3 machine-learning algorithms: naive Bayes, decision trees, and artificial neural networks. The models were trained and tested on data from complete blood count (CBC) and serum chemistry (SC) results for the following 3 groups of client-owned cats: normal, inflammatory bowel disease (IBD), or alimentary lymphoma (ALA). Naive Bayes and artificial neural networks achieved higher classification accuracy (sensitivities of 70.8% and 69.2%, respectively) than the decision tree algorithm (63%, p < 0.0001). The areas under the receiver-operating characteristic curve for classifying cases into the 3 categories was 83% by naive Bayes, 79% by decision tree, and 82% by artificial neural networks. Prediction models using machine learning provided a method for distinguishing between ALA–IBD, ALA–normal, and IBD–normal. The naive Bayes and artificial neural networks classifiers used 10 and 4 of the CBC and SC variables, respectively, to outperform the C4.5 decision tree, which used 5 CBC and SC variables in classifying cats into the 3 classes. These models can provide another noninvasive diagnostic tool to assist clinicians with differentiating between IBD and ALA, and between diseased and nondiseased cats.

Objective: This study evaluated an existing SNOMED-CT model for structured recording of heart murmur findings and compared it to a concept-dependent attributes model using content from SNOMED-CT. Methods: The authors developed a model for recording heart murmur findings as an alternative to SNOMED-CT's use of Interprets and Has interpretation. A micro-nomenclature was then created to support each model using subset and extension mechanisms described for SNOMED-CT. Each micro-nomenclature included a partonomy of cardiac cycle timing values. A mechanism for handling ranges of values was also devised. One hundred clinical heart murmurs were recorded using purpose-built recording software based on both models. Results: Each micro-nomenclature was extended through the addition of the same list of concepts. SNOMED role grouping was required in both models. All 100 clinical murmurs were described using each model. The only major differences between the two models were the number of relationship rows required for storage and the hierarchical assignments of concepts within the micro-nomenclatures. Conclusion: The authors were able to capture 100 clinical heart murmurs with both models. Requirements for implementing the two models were virtually identical. In fact, data stored using these models could be easily inter- converted. There is no apparent penalty for implementing either approach. j J Am Med Inform Assoc. 2006;13:321-333. DOI 10.1197/jamia.M1973.

Objective—To determine whether pharmacokinetic analysis of data derived from a single IV dose of iohexol could be used to predict creatinine clearance and evaluate simplified methods for predicting serum clearance of iohexol with data derived from 2 or 3 blood samples in clinically normal foals. Animals—10 healthy foals. Procedure—Serum disposition of iohexol and exogenous creatinine clearance was determined simultaneously in each foal (5 males and 5 females). A 3-compartment model of iohexol serum disposition was selected via standard methods. Iohexol clearance calculated from the model was compared with creatinine clearance. Separate limited-sample models were created with various combinations of sample times from the terminal slope of the plasma versus time profile for iohexol. Correction factors were determined for the limited-sample models, and iohexol clearance calculated via each method was compared with exogenous creatinine clearance by use of method comparison techniques. Results—Mean exogenous creatinine clearance was 2.17 mL/min/kg. The disposition of iohexol was best described by a 3-compartment open model. Mean clearance value for iohexol was 2.15 mL/min/kg and was not significantly different from mean creatinine clearance. A method for predicting serum iohexol clearance based on a 2-sample protocol (3- and 4-hour samples) was developed. Conclusions and Clinical Relevance—Iohexol clearance can be used to predict exogenous creatinine clearance and can be determined from 2 blood samples taken after IV injection of iohexol. Appropriate correction factors for adult horses and horses with abnormal glomerular filtration rate need to be determined. (Am J Vet Res 2003;64:1486–1490)

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.

The objective of this study was to examine the bronchodilating effect of an inhaled long acting beta2-agonist (salmeterol) after a high dose of an inhaled short acting beta2-agonist (salbutamol) in asthma patients. We used a randomized double-blind, placebo-controlled, crossover design, studying seven subjects with moderate asthma, treated with inhaled steroids and highly reversible to salbutamol and salmeterol. 1.5 h after salmeterol inhalation, the mean difference in FEV1 between salbutamol and placebo pretreatment days was 6.31% and ranged from 0.02 to 1.05%, 2.5-10.5 h after salmeterol inhalation. We concluded that the effect measured as the duration of bronchodilation of salmeterol is not decreased by previously inhaled salbutamol. We only found a trend toward an additive effect of combining salbutamol and salmeterol, probably because the high dose of salbutamol did not give room for further improvement in FEV1. In accordance with other clinical studies we were unable to demonstrate any clinical implications of the salmeterol partial beta2-antagonism known from animal and in vitro studies.

The response of peripheral blood vessels to adrenergic and cholinergic agonists was examined 1, 3, 7, and 21 d after hens were treated with a single intramuscular injection of 2.5 mg/kg cyclic phenyl saligenin phosphate (PSP) or 0.10 mg/kg paraoxon (PXN). These two organophosphates (OPs) cause different clinical effects in exposed animals, as PSP causes organophosphate-induced delayed neuropathy (OPIDN) and PXN causes acute poisoning through inhibition of acetylcholinesterase. For these studies, the ischiadic artery was cannulated both prograde and retrograde and the blood was shunted through a pump to maintain a constant flow. Alterations in pressure measured at the pump outflow were used to indicate changes in limb vascular resistance. Dose-response curves were generated for the response to intravenous administration of acetylcholine (ACh), phenylephrine (PE), or salbutamol (SAL) (10(-8) to 10(-4) mol/kg). Acetylcholine at 10(-8) to 10(-7) mol/kg caused an increase in vascular resistance, whereas concentrations of 10(-5) to 10(-4) mol/kg caused a decrease in vascular resistance in hens given PSP 1 and 3 d previously. The response of PXN-treated hens to ACh was not significantly altered from that of vehicle-treated hens. The resistance generated in response to PE, an alpha 1-adrenergic agonist, in PSP-treated hens was greater than levels in vehicle-treated hens on d 1 and 3 and greater than the response seen in hens treated with PXN. Salbutamol, a beta 2-adrenergic agonist, at concentrations of 10(-7) to 10(-4) mol/kg caused an increase in resistance 1 and 3 d after PSP and a decrease on d 7. The responses to SAL were different in PXN-treated hens, as these hens demonstrated a lesser increase in resistance at concentrations of 10(-8) to 10(-7) mol/kg and a decrease in resistance at 10(-5) to 10(-4) mol/kg 1 d after administration of PXN. These observations indicate that response to vasoactive agents is altered in OP-treated hens and that responses differ between a compound capable of causing OPIDN (PSP) and a compound that only causes acute effects (PXN).

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.

Carbaryl, a carbamate insecticide, exerts its toxic effect in animals by inhibiting the activity of neural acetylcholinesterase. Differences in sensitivity of this enzyme to inhibition were studied after intraperitoneal administration to chickens and rats. A dose of 900 mg/kg to chickens and 70 mg/kg to rats caused equivalent inhibition of brain cholinesterase activities (57% +/- 6 and 47% +/- 4, respectively) 60 min after administration, which was the time of maximal cholinergic signs. Signs of toxicity (salivation, respiratory distress, muscle tremors and weakness) were more pronounced in rats than in chickens when brain acetylcholinesterase was inhibited to the same extent in both species. Carboxylesterase activities in brain, liver, and plasma were also inhibited 60 min after administration of carbaryl to chickens and rats. Activities of enzymes associated with hepatic microsomes were unaffected. Specific activities of brain esterases, including acetylcholinesterase, carboxylesterase and neurotoxic esterase, were higher in untreated chickens than in untreated rats. Specific activities of liver esterases (carboxylesterase, A-esterase) were, however, 4- and 10-fold lower in untreated chickens than in untreated rats. Total clearance of carbaryl in the chicken, determined after intravenous administration of 5 mg/kg, was 0.26 +/- 0.02 l/kg/min. This value is 5.7 times higher than that reported for the rat, indicating that the relatively lower activities of esterases in the liver of chickens did not affect the clearance of this chemical in the avian species.

In 10 healthy subjects, the influence of acute alcohol intake on the pharmacokinetics of isoniazid (INH) was studied.To test the hypothesis that alcohol increases the conversion of INH by acetylation into its metabolite acetylisoniazid.In a crossover design, an oral dose of 300 mg INH was administered on 2 separate days, 14 days apart, with or without alcohol to a serum alcohol of about 21 mmol/l (1 g/l) maintained for 12 h.Neither the metabolism of INH nor that of acetylisoniazid was changed by acute alcohol intake.Acute alcohol intake has no impact on the conversion of INH to its metabolite acetylisoniazid, which is catalysed by the enzyme N-acetyltranferase. Accordingly, a metabolic effect of acute alcohol intake on INH metabolism probably contributes little to the therapeutic failure of anti-tuberculosis treatment among alcoholics.

Objective— To evaluate effects of fenoldopam on renal function in normal dogs subjected to bisection nephrotomy. In addition, effects of bisection nephrotomy on renal function in normal dogs were evaluated. Study Design— Controlled, randomized, blinded experiment. Sample Population— Sixteen mixed-breed adult dogs. Methods— Dogs were paired for sex, body weight, and approximate age and assigned to 1 of 2 groups: fenoldopam (F) or placebo (P). Baseline glomerular filtration rate (GFR) based on quantitative renal scintigraphy using 99mTc-DTPA, blood urea nitrogen (BUN), serum creatinine (SCr), urinalysis, and urine culture were performed before surgery. Left nephrotomy was performed via median celiotomy. Group F dogs were administered intravenous (IV) fenoldopam (0.1 μg/kg/min) for 90 minutes, whereas group P dogs were administered an equivalent volume of saline (0.9 % NaCl) solution for 90 minutes. Temperature, heart rate, respiration, direct arterial blood pressure, and urine volume were recorded during anesthesia. Renal function was assessed by measuring SCr, BUN, and GFR at 1, 21, and 42 days after surgery. Results— There was no significant difference between groups in measured physiologic variables. No significant difference in GFR, BUN, or SCr between groups or between operated or control kidneys was detected. Conclusions— Bisection nephrotomy in normal dogs with renal arterial occlusion of 15 minutes and using a simple continuous capsular closure does not adversely affect renal function. Clinical Relevance— Bisection nephrotomy, as described in this study, does not decrease renal function; perioperative administration of renoprotective agents is not necessary in normal dogs.

In the light of the current American epidemic, and since West Nile fever (WNF) has never previously been reported in Denmark, we describe two cases imported from Israel and Canada, respectively. WNF was diagnosed in a 46-year-old Danish tourist returning from Israel and a visiting 73-year-old Canadian citizen with Danish ancestry. The former manifested itself clinically as a mild flu-like illness, the latter as serious infection of the central nervous system. Thus, in addition to representing a rare case of West Nile encephalitis, it also constitutes one of the first reported cases of human infection of Canadian origin.

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.

To determine pharmacokinetic variables that describe disposition of ketoprofen after its i.v. administration to foals24 hours old.6 healthy foals (1 male and 5 females); mean age, 12.5 (range, 8.5 to 17) hours at time of dose administration.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.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 foals24 hours old was 4.3 hours.Although additional factors, such as dehydration or sepsis, must be considered on a case-by-case basis, the dose of ketoprofen administered to foals24 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.

To determine pharmacokinetic variables that describe the disposition of flunixin after i.v. administration of flunixin meglumine to foals24 hours old.6 healthy foals, 2 males and 4 females (mean age, 11.6 hours; range, 6 to 22.5 hours).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.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 foals24 hours old was 8.5 hours.Although additional factors (eg, dehydration or sepsis) must be considered on a case-by-case basis, flunixin meglumine should be administered differently to foals24 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.

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.

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 (P0.01) 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 (P0.001) greater than AUC on day 44 (1.66 +/- 0.308 ng.min/ml). Oral clearance was significantly (P0.01) 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.

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.

In a recent JAMIA article,1 Deepthi Rajeeve asserts that ‘some of the existing concepts [in SNOMED CT] do not meet the case definition and do not represent reportable conditions because non-human conditions are included as children in the hierarchy’, specifically citing campylobacteriosis and porcine intestinal adenomatosis. The authors suggest creating a SNOMED CT hierarchy that is exclusively human conditions. First we must point out that the term they selected (campylobacteriosis) does not mean ‘campylobacter-induced disease in human beings’. Campylobacteriosis means (in SNOMED CT and in the real world) ‘disorder characterized by infection by any campylobacter species’. No information on the species affected is or should be implied. In fact, we believe that several disorders in this hierarchy, including the cited ‘porcine enteric adenomatosis’, are likely to be overspecified by the inclusion of species. Inclusion of species in the naming of disorders is an artifact of usage patterns that does not allow for the fact that many …

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.

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.

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.

One aspect of the rapid advances in molecular genetics is the capacity to identify genetic predispositions in a particular individual, where previously we made risk assessments based on aggregate or population observations. 1 2 Specific genetic data on one person unavoidably involve the family. They reveal information not only about the person examined but about their relatives and future children, who may be sick or carriers of the disease or trait. The proband, the family, and the genetic counsellor are faced with the problem of communicating news of the high risk for a genetic disease to healthy (asymptomatic) family members. They are also faced with making a moral choice between the right of family members to be privy to this information and their right to “blissful ignorance.” #### Summary points Most genetic counsellors believe that family members have a moral obligation to share genetic information with each other.3 Many counsellors also believe that an uninvited approach to relatives at risk for a genetic disease is ethically questionable, irrespective of the disease. The Danish Ethics Council recently stated that “no unsolicited approach may be made by the health authorities in the case of an examination that may show any hereditary disease in the family. This should also be the case in situations where it can …

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.

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.

We consider three broad classes of nonstandard models for b quark decay: (1) b → llq with charged or neutral leptons of arbitrary flavor; (2) b → l q q ; and (3) b → qa − where a − is a Higgs boson or hyperpion. For these classes of models we have calculated the charged energy fraction and the inclusive yields of electrons, muons, protons, and lambdas. We demonstrate that these model predictions are inconsistent with CLEO measurements at the γ (4S).

Using the CLEO detector at the Cornell Electron Storage Ring, the authors have measured the leptonic branching fraction, B/sub mumu/, of the UPSILON(1S), UPSILON(2S), and UPSILON(3S) to be 2.7 +- 0.3 +- 0.3%, 1.9 +- 1.3 +- 0.5%, and 3.3 +- 1.3 +- 0.7%, respectively. Combining these values of B/sub mumu/ with previous measurements of the leptonic widths of these resonances, the authors find the total width of the UPSILON(1S), UPSILON(2S), and UPSILON(3S) to be 48 +- 4 +- 4, 27 +- 17 +- 6, and 13 +- 4 +- 3 keV.

We have studied the production of B mesons in e/sup +/e/sup -/ annihilations and present new measurements of the semileptonic branching fractions for B-meson decay. We find B(B..-->..e..nu..X) = 0.127 +- 0.017 +- 0.013 and B(B..--> mu nu..X) = 0.122 +- 0.017 +- 0.031, where the errors are statistical and systematic, respectively. The observed lepton momentum spectra from B decays are presented. From these spectra we find the mean hadronic mass (M/sub X/) recoiling against the detected lepton to be M/sub X/ = 2.2 +- 0.2 GeV/c/sup 2/. We have also observed an enhancement in the lepton yield from the continuum above BB-bar threshold. This enhancement is interpreted as continuum B production and is consistent with what is expected from the naive quark model.

We describe the performance of the pressurized d E /d x system of the CLEO detector. We show resolution and relativistic rise measurements. The system has been used to identify low momentum hadrons, high momentum electrons and measure the pion fraction at high momentum.

A detailed investigation of the decay UPSILON(2S)..--> pi../sup +/..pi../sup -/UPSILON(1S) has been made from 128 000 UPSILON(2S) decays observed in the CLEO detector at the Cornell Electron Storage Ring (CESR). We find this branching ratio to be (19.1 +- 1.2 +- 0.6)%. The properties of the ..pi pi.. system have been studied using 491 exclusive events of the type UPSILON(2S)..--> pi../sup +/..pi../sup -/UPSILON(1S), UPSILON(1S)..-->..e/sup +/e/sup -/ or ..mu../sup +/..mu../sup -/. Assuming e-..mu.. universality we find B(UPSILON(1S)..--> mu../sup +/..mu../sup -/) = (2.84 +- 0.18 +- 0.20)%. A search for UPSILON(2S)..-->..etaUPSILON(1S) yields an upper limit of 1% at the 90% confidence level for this branching ratio. We have also searched for (UPSILON(2S) or UPSILON(3S))..--> pi../sup +/..pi../sup -/UPSILON(1S), UPSILON(1S)..-->..noninteracting particles.

Pharmacological information has been organized and encoded in rules and frames for systematic retrieval. This includes: delineation, definition, and hierarchical subdivision of mechanisms responsible for drug interactions; division of pharmacological agents into a hierarchy of subclasses to allow for defining interacting drugs by classes as well as by specific agents; correlation of drug classes and specific drugs with mechanisms by which they may be involved in drug interactions. This information, accessible through a natural language-like and menu driven interface, allows clinicians to know what may happen when two drugs are used together, why, what can be done to alleviate detrimental interactions, and what related drugs may also be involved in similar interactions.

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.

A measurement is presented of the inclusive production of charged ${D}^{*}$ and neutral $D$ mesons from nonresonant ${e}^{+}{e}^{\ensuremath{-}}$ annihilation in the energy region near the $\ensuremath{\Upsilon}(4S)$ resonance. The momentum distribution shows a large contribution at high momenta as expected for heavy quark production. Comparison of the spectrum with several phenomenological models is made. The relative yields of the ${D}^{*}$ and $D$ mesons indicate that the charm cross section is dominated by the ${D}^{*}$ contribution.

We have searched in the decays of the ϒ(1S), ϒ(2S) and B mesons for the narrow state, γ, seen by the Mark II group in radiative ψ decay. We find the product branching fractions B[ϒ(1S) → γγ]·B[γ → K+K−], B[ϒ(2S) → γ γ]· B[γ → K+K−] and B[B → γX]·B[γ → K+K−] to be less than 2×10−4, 9×10−5 and 3×10−3, respectively at 90% confidence level. These limits constrain theoretical models if the γ is interpreted as a Higgs boson.

We report measurements made with the CLEO detector at the Cornell Electron Storage Ring (CESR) of the total cross section for ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}\mathrm{hadrons}$ at the $\ensuremath{\Upsilon}(1S)$, $\ensuremath{\Upsilon}(2S)$, and $\ensuremath{\Upsilon}(3S)$, and in the nearby nonresonant continuum. We find $R=3.77\ifmmode\pm\else\textpm\fi{}0.06 (\mathrm{statistical}) \ifmmode\pm\else\textpm\fi{} 0.24 (\mathrm{systematic})$ for the ratio of the nonresonant hadronic cross section to the cross section for muon-pair production at a center-of-mass total energy $W=10.4$ GeV. For the leptonic decay widths ${\ensuremath{\Gamma}}_{\mathrm{ee}}$ of the $\ensuremath{\Upsilon}(1S)$, $\ensuremath{\Upsilon}(2S)$, and $\ensuremath{\Upsilon}(3S)$ we obtain 1.30\ifmmode\pm\else\textpm\fi{}0.05\ifmmode\pm\else\textpm\fi{}0.08, 0.52\ifmmode\pm\else\textpm\fi{}0.03\ifmmode\pm\else\textpm\fi{}0.04, and 0.42\ifmmode\pm\else\textpm\fi{}0.04\ifmmode\pm\else\textpm\fi{}0.03 keV, respectively.

$B$-meson decays to final states consisting of a ${D}^{0}$ or ${D}^{*\ifmmode\pm\else\textpm\fi{}}$ and one or two charged pions have been observed. The charged-$B$ mass is 5270.8 \ifmmode\pm\else\textpm\fi{} 2.3 \ifmmode\pm\else\textpm\fi{} 2.0 MeV and the neutral-$B$ mass is 5274.2 \ifmmode\pm\else\textpm\fi{} 1.9 \ifmmode\pm\else\textpm\fi{} 2.0 MeV.

We have observed the decay of the UPSILON(2S) into the UPSILON(1S), obtaining a branching ratio of 19.1 +- 3.1 +- 2.9% for the mode UPSILON(2S)..--> pi../sup +/..pi../sup -/UPSILON(1S). The di-pion mass spectrum peaks at large invariant mass, and the angular distribution of the di-pion system is consistent with s-wave production.

We report measurements from CLEO detector of the rate of ..xi.. and ..lambda.. production in e/sup +/e/sup -/ interactions in the upsilon region. Hyperon production from the decay of the UPSILON(1S) is compared with continuum e/sup +/e/sup -/ data. The ratio of the production rates of ..lambda.. (and Lambda-bar) to K/sup 0/ (and K-bar /sup 0/) on the UPSILON(1S) is 0.21 +- 0.03, much larger than in the continuum, 0.07 +- 0.01. The ratios of the production rates of the ..xi.. and the ..lambda.. are comparable, 0.10 +- 0.02 (UPSILON(1S)) and 0.07 +- 0.02 (continuum). We discuss some implications of the data for gluon and quark fragmentation models.

The branching ratio of UPSILON(3S)..--> pi../sup +/..pi../sup -/UPSILON(1S) has been measured to be (4.9 +- 0.9 +- 0.5)%. The di-pion invariant-mass distribution for this decay is flatter than that for the decays UPSILON(2S)..--> pi../sup +/..pi../sup -/UPSILON(1S) and psi'..--> pi../sup +/..pi../sup -/psi.

Evidence is presented for a narrow meson resonance of mass 1970\ifmmode\pm\else\textpm\fi{}5\ifmmode\pm\else\textpm\fi{}5 MeV produced in continuum ${e}^{+}{e}^{\ensuremath{-}}$ annihilations at $\sqrt{s}$ of 10.5 GeV, and decaying into a $\ensuremath{\phi}$ and a charged $\ensuremath{\pi}$.

The inclusive branching fraction for B-meson decay into D/sup 0/ mesons and the momentum spectrum of the D/sup 0/'s have been measured. 0.8 +- 0.2 +- 0.2 D/sup 0/ per B decay was found. The shape of the spectrum suggests an interesting picture of B-meson decay.